CD3G

UniProt ID: P09693
Organism: Homo sapiens
Review Status: DRAFT
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Gene Description

CD3G encodes CD3 gamma, a single-pass signaling subunit of the T cell antigen receptor. Its extracellular immunoglobulin-like domain pairs noncovalently with CD3 epsilon, and extracellular and transmembrane contacts help organize the receptor complex. Human alpha-beta and reconstituted gamma-delta TCR complexes contain this gamma-epsilon module. The cytoplasmic tail carries one ITAM whose phosphorylation permits signaling-effector recruitment, including ZAP70, while a separate dileucine sorting signal engages endocytic adaptors and helps control receptor internalization. CD3 gamma promotes normal surface receptor abundance and efficient ligand- or PKC-stimulated trafficking; some mature human T cells retain surface receptors and constitutive internalization without it. Biallelic defects cause variable immunodeficiency, sometimes accompanied by autoimmunity and altered regulatory-T-cell function.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0002250 adaptive immune response
NAS
PMID:29789755
Regulatory mechanisms in T cell receptor signalling.
ACCEPT
Summary: CD3G participates in adaptive T cell responses as a receptor signaling subunit.
Reason: The cited review concerns TCR signaling; the human CD3G assembly and deficiency evidence independently establishes the subunit role. This accepts the author-statement process without claiming that the review performs a CD3G-specific experiment.
GO:0002250 adaptive immune response
NAS
PMID:30976362
T cell receptor signaling for Ξ³Ξ΄T cell development.
ACCEPT
Summary: CD3G contributes to adaptive responses of gamma-delta T cells.
Reason: The gamma-delta signaling review is consistent with a physical CD3G-containing receptor complex. Reconstituted human gamma-delta structures provide separate human composition evidence; mouse-only stoichiometry is not generalized to all human receptors.
Supporting Evidence:
GO:0004888 transmembrane signaling receptor activity
IBA
GO_REF:0000033
ACCEPT
Summary: CD3G supplies a signal-transducing component of the transmembrane TCR complex.
Reason: Retain the curated PAINT inheritance, corroborated by human assembly and ITAM evidence. The actual PTN000060280 IBD placement was not reconstructed; donor count and the target itself in WITH/FROM do not undermine it. Ligand specificity resides in the clonotypic TCR chains; the core states the complex contribution explicitly.
Supporting Evidence:
GO_REF:0000033
GO:0004888 transmembrane signaling receptor activity
IC
PMID:9485181
Assembly of the TCR/CD3 complex: CD3 epsilon/delta and CD3 e...
ACCEPT
Summary: CD3G contributes to the assembled transmembrane signaling receptor.
Reason: The IC inference from alpha-beta TCR membership agrees with human CD3 gamma-epsilon association. The historical double-TCR model in the cited paper is not adopted: the later human structure resolves one alpha-beta pair with the signaling dimers. No intrinsic peptide-MHC recognition by CD3G is asserted.
Supporting Evidence:
GO:0004888 transmembrane signaling receptor activity
IEA
GO_REF:0000002
ACCEPT
Summary: The CD3-family domain mapping is consistent with receptor signal transduction.
Reason: InterPro supplies an electronic association; human complex structure and phosphorylated ITAM binding provide target evidence for the signaling-subunit role. Preserve enables in the source object, while distinguishing the complex contribution in the core.
Supporting Evidence:
GO_REF:0000002
GO:0004888 transmembrane signaling receptor activity
IMP
PMID:12794121
TCR dynamics in human mature T lymphocytes lacking CD3 gamma...
ACCEPT
Summary: Human CD3G supports normal surface TCR assembly and signaling competence.
Reason: The human deficiency and retroviral-restoration study supports a functional receptor subunit. Residual surface TCR persists without CD3G, so the evidence does not establish an absolute assembly requirement in every mature T cell or direct antigen binding by CD3G.
Supporting Evidence:
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
KEEP AS NON CORE
Summary: The curated human interaction with TMEM262 is retained as a non-core association.
Reason: The exact E9PQX1 edge is recorded in GOA and the reviewed UniProt interaction list. The complete HuRI abstract establishes the screen context, but its original target construct/table was not independently inspected. No evidence supports calling this edge false or merely membrane-protein background. Retain the qualitative binding under the project instruction; partner identity alone does not establish a more specific interface or adaptor function.
Supporting Evidence:
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
KEEP AS NON CORE
Summary: The curated human interaction with LAT isoform 2 is retained as a non-core association.
Reason: The exact O43561-2 edge is recorded in GOA and the reviewed UniProt interaction list. The complete HuRI abstract establishes the screen context, but its original target construct/table was not independently inspected. No evidence supports calling this edge false or merely membrane-protein background. Retain the qualitative binding under the project instruction; partner identity alone does not establish a more specific interface or adaptor function.
Supporting Evidence:
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
KEEP AS NON CORE
Summary: The curated human interaction with MAL is retained as a non-core association.
Reason: The exact P21145 edge is recorded in GOA and the reviewed UniProt interaction list. The complete HuRI abstract establishes the screen context, but its original target construct/table was not independently inspected. No evidence supports calling this edge false or merely membrane-protein background. Retain the qualitative binding under the project instruction; partner identity alone does not establish a more specific interface or adaptor function.
Supporting Evidence:
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
KEEP AS NON CORE
Summary: The curated human interaction with EMP1 is retained as a non-core association.
Reason: The exact P54849 edge is recorded in GOA and the reviewed UniProt interaction list. The complete HuRI abstract establishes the screen context, but its original target construct/table was not independently inspected. No evidence supports calling this edge false or merely membrane-protein background. Retain the qualitative binding under the project instruction; partner identity alone does not establish a more specific interface or adaptor function.
Supporting Evidence:
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
KEEP AS NON CORE
Summary: The curated human interaction with PMP22 is retained as a non-core association.
Reason: The exact Q01453 edge is recorded in GOA and the reviewed UniProt interaction list. The complete HuRI abstract establishes the screen context, but its original target construct/table was not independently inspected. No evidence supports calling this edge false or merely membrane-protein background. Retain the qualitative binding under the project instruction; partner identity alone does not establish a more specific interface or adaptor function.
Supporting Evidence:
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
KEEP AS NON CORE
Summary: The curated human interaction with KTN1 isoform 3 is retained as a non-core association.
Reason: The exact Q86UP2-3 edge is recorded in GOA and the reviewed UniProt interaction list. The complete HuRI abstract establishes the screen context, but its original target construct/table was not independently inspected. No evidence supports calling this edge false or merely membrane-protein background. Retain the qualitative binding under the project instruction; partner identity alone does not establish a more specific interface or adaptor function.
Supporting Evidence:
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
KEEP AS NON CORE
Summary: The curated human interaction with TMEM54 is retained as a non-core association.
Reason: The exact Q969K7 edge is recorded in GOA and the reviewed UniProt interaction list. The complete HuRI abstract establishes the screen context, but its original target construct/table was not independently inspected. No evidence supports calling this edge false or merely membrane-protein background. Retain the qualitative binding under the project instruction; partner identity alone does not establish a more specific interface or adaptor function.
Supporting Evidence:
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
KEEP AS NON CORE
Summary: The curated human interaction with TMEM203 is retained as a non-core association.
Reason: The exact Q969S6 edge is recorded in GOA and the reviewed UniProt interaction list. The complete HuRI abstract establishes the screen context, but its original target construct/table was not independently inspected. No evidence supports calling this edge false or merely membrane-protein background. Retain the qualitative binding under the project instruction; partner identity alone does not establish a more specific interface or adaptor function.
Supporting Evidence:
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
KEEP AS NON CORE
Summary: The curated human interaction with TMEM19 is retained as a non-core association.
Reason: The exact Q96HH6 edge is recorded in GOA and the reviewed UniProt interaction list. The complete HuRI abstract establishes the screen context, but its original target construct/table was not independently inspected. No evidence supports calling this edge false or merely membrane-protein background. Retain the qualitative binding under the project instruction; partner identity alone does not establish a more specific interface or adaptor function.
Supporting Evidence:
GO:0005886 plasma membrane
EXP
PMID:8636209
Role of CD3 gamma in T cell receptor assembly.
ACCEPT
Summary: Human CD3G reaches the cell surface within assembled TCR complexes.
Reason: The human CD3G mutational assembly study supports the curated membrane localization. Its abstract directly tests CD3G extracellular and transmembrane regions; this is not an inference from an unrelated paralog title.
Supporting Evidence:
GO:0005886 plasma membrane
IDA
GO_REF:0000052
ACCEPT
Summary: Plasma-membrane localization is supported independently of the imaging curation.
Reason: The GO_REF identifies immunofluorescence curation, without exposing its target image here. Human receptor assembly and surface-labeling evidence separately supports this location, so no original image inspection is implied.
Supporting Evidence:
GO_REF:0000052
GO:0005886 plasma membrane
IDA
PMID:11390434
The transmembrane adaptor protein TRIM regulates T cell rece...
ACCEPT
Summary: CD3G is present in surface-labeled human TCR complexes.
Reason: Selected original Methods and Results include surface biotinylation of Jurkat cells, anti-CD3 immunoprecipitation and CD3 gamma reprecipitation. The TRIM-focused title does not exclude the assayed target. Preserve the source is_active_in qualifier without assigning TRIM-dependent calcium effects to CD3G.
Supporting Evidence:
GO:0005886 plasma membrane
IDA
PMID:31461748
Structural basis of assembly of the human T cell receptor-CD...
ACCEPT
Summary: The human TCR structure locates CD3G across the membrane.
Reason: The directly characterized complex includes the CD3 gamma-epsilon pair with transmembrane contacts. It supports membrane localization and assembly, without assigning the antigen-binding surface to CD3G.
Supporting Evidence:
GO:0005886 plasma membrane
IEA
GO_REF:0000044
ACCEPT
Summary: The UniProt subcellular-location mapping correctly places CD3G at the plasma membrane.
Reason: The reviewed single-pass topology and human surface receptor data agree with the conservative SL-0039 mapping.
Supporting Evidence:
GO_REF:0000044
GO:0005886 plasma membrane
NAS
PMID:30976362
T cell receptor signaling for Ξ³Ξ΄T cell development.
ACCEPT
Summary: CD3G is a membrane component of gamma-delta TCR complexes.
Reason: The review attribution is corroborated by separate human gamma-delta TCR-CD3 structures. This is a location assertion, not a claim that every species uses the same dimer stoichiometry.
Supporting Evidence:
GO:0005886 plasma membrane
NAS
PMID:9485181
Assembly of the TCR/CD3 complex: CD3 epsilon/delta and CD3 e...
ACCEPT
Summary: The associated CD3 gamma-epsilon module is part of the surface TCR.
Reason: Human Jurkat/thymocyte association data and the later human structural complex support the location. The earlier proposed double-TCR stoichiometry is not required for it.
Supporting Evidence:
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-198955
ACCEPT
Summary: The Reactome antigen-presenting MHC class I engagement context retains plasma-membrane CD3G.
Reason: This source row asserts compartment membership of the receptor-containing assembly. Human surface and structural evidence supports that compartment; the event does not make CD3G the kinase, phosphatase, ligand-binding TCR chain or the other protein named in its title.
Supporting Evidence:
Reactome:R-HSA-198955
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-202165
ACCEPT
Summary: The Reactome ITAM phosphorylation context retains plasma-membrane CD3G.
Reason: This source row asserts compartment membership of the receptor-containing assembly. Human surface and structural evidence supports that compartment; the event does not make CD3G the kinase, phosphatase, ligand-binding TCR chain or the other protein named in its title.
Supporting Evidence:
Reactome:R-HSA-202165
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-202168
ACCEPT
Summary: The Reactome LCK-dependent ZAP70 phosphorylation context retains plasma-membrane CD3G.
Reason: This source row asserts compartment membership of the receptor-containing assembly. Human surface and structural evidence supports that compartment; the event does not make CD3G the kinase, phosphatase, ligand-binding TCR chain or the other protein named in its title.
Supporting Evidence:
Reactome:R-HSA-202168
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-202174
ACCEPT
Summary: The Reactome ZAP70 activation context retains plasma-membrane CD3G.
Reason: This source row asserts compartment membership of the receptor-containing assembly. Human surface and structural evidence supports that compartment; the event does not make CD3G the kinase, phosphatase, ligand-binding TCR chain or the other protein named in its title.
Supporting Evidence:
Reactome:R-HSA-202174
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-202214
ACCEPT
Summary: The Reactome CD45-dependent LCK dephosphorylation context retains plasma-membrane CD3G.
Reason: This source row asserts compartment membership of the receptor-containing assembly. Human surface and structural evidence supports that compartment; the event does not make CD3G the kinase, phosphatase, ligand-binding TCR chain or the other protein named in its title.
Supporting Evidence:
Reactome:R-HSA-202214
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-202216
ACCEPT
Summary: The Reactome SLP76 phosphorylation context retains plasma-membrane CD3G.
Reason: This source row asserts compartment membership of the receptor-containing assembly. Human surface and structural evidence supports that compartment; the event does not make CD3G the kinase, phosphatase, ligand-binding TCR chain or the other protein named in its title.
Supporting Evidence:
Reactome:R-HSA-202216
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-202233
ACCEPT
Summary: The Reactome CSK-dependent LCK inactivation context retains plasma-membrane CD3G.
Reason: This source row asserts compartment membership of the receptor-containing assembly. Human surface and structural evidence supports that compartment; the event does not make CD3G the kinase, phosphatase, ligand-binding TCR chain or the other protein named in its title.
Supporting Evidence:
Reactome:R-HSA-202233
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-202245
ACCEPT
Summary: The Reactome LAT phosphorylation context retains plasma-membrane CD3G.
Reason: This source row asserts compartment membership of the receptor-containing assembly. Human surface and structural evidence supports that compartment; the event does not make CD3G the kinase, phosphatase, ligand-binding TCR chain or the other protein named in its title.
Supporting Evidence:
Reactome:R-HSA-202245
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-202248
ACCEPT
Summary: The Reactome PLCG1 phosphorylation context retains plasma-membrane CD3G.
Reason: This source row asserts compartment membership of the receptor-containing assembly. Human surface and structural evidence supports that compartment; the event does not make CD3G the kinase, phosphatase, ligand-binding TCR chain or the other protein named in its title.
Supporting Evidence:
Reactome:R-HSA-202248
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-202291
ACCEPT
Summary: The Reactome LCK activation context retains plasma-membrane CD3G.
Reason: This source row asserts compartment membership of the receptor-containing assembly. Human surface and structural evidence supports that compartment; the event does not make CD3G the kinase, phosphatase, ligand-binding TCR chain or the other protein named in its title.
Supporting Evidence:
Reactome:R-HSA-202291
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-202307
ACCEPT
Summary: The Reactome PKC-theta conformational activation context retains plasma-membrane CD3G.
Reason: This source row asserts compartment membership of the receptor-containing assembly. Human surface and structural evidence supports that compartment; the event does not make CD3G the kinase, phosphatase, ligand-binding TCR chain or the other protein named in its title.
Supporting Evidence:
Reactome:R-HSA-202307
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-202344
ACCEPT
Summary: The Reactome ZAP70 recruitment context retains plasma-membrane CD3G.
Reason: This source row asserts compartment membership of the receptor-containing assembly. Human surface and structural evidence supports that compartment; the event does not make CD3G the kinase, phosphatase, ligand-binding TCR chain or the other protein named in its title.
Supporting Evidence:
Reactome:R-HSA-202344
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-2029268
ACCEPT
Summary: The plasma-membrane assertion is retained; the PLCG activation context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-2029268
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-2029270
ACCEPT
Summary: The plasma-membrane assertion is retained; the PLCG membrane recruitment context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-2029270
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-2029271
ACCEPT
Summary: The plasma-membrane assertion is retained; the PI3K lipid phosphorylation context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-2029271
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-2029272
ACCEPT
Summary: The plasma-membrane assertion is retained; the PLCG release context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-2029272
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-2029273
ACCEPT
Summary: The plasma-membrane assertion is retained; the PI3K-SYK association context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-2029273
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-2029451
ACCEPT
Summary: The plasma-membrane assertion is retained; the VAV-dependent RAC1 activation context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-2029451
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-2029452
ACCEPT
Summary: The plasma-membrane assertion is retained; the SYK recruitment context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-2029452
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-2029453
ACCEPT
Summary: The plasma-membrane assertion is retained; the VAV phosphorylation context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-2029453
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-2029455
ACCEPT
Summary: The plasma-membrane assertion is retained; the FCGRIA cross-linking context is bounded.
Reason: Official Reactome R-HSA-2029455 describes the Fc receptor gamma chain, yet its input chain R-HSA-2029093 to R-HSA-1861690 to R-HSA-197917 explicitly links CD3G/P09693. Official FCER1G identity is instead P30273. This is a concrete source-mapping inconsistency, not evidence against independently established CD3G plasma-membrane localization. Preserve the original TAS source and retain the location using the human TCR evidence, without adopting Fc-receptor participation.
Supporting Evidence:
Reactome:R-HSA-2029455
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-2029457
ACCEPT
Summary: The plasma-membrane assertion is retained; the FCGRIIIA cross-linking context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-2029457
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-2029458
ACCEPT
Summary: The plasma-membrane assertion is retained; the VAV1 recruitment context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-2029458
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-2029459
ACCEPT
Summary: The plasma-membrane assertion is retained; the Fc receptor partitioning/phosphorylation context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-2029459
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-2029467
ACCEPT
Summary: The plasma-membrane assertion is retained; the CRKII-DOCK180-ELMO-dependent RAC1 activation context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-2029467
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-2029476
ACCEPT
Summary: The plasma-membrane assertion is retained; the myosin-associated phagosome formation context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-2029476
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-2197697
ACCEPT
Summary: The plasma-membrane assertion is retained; the CRKII-DOCK180-ELMO recruitment context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-2197697
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-389758
ACCEPT
Summary: The Reactome PD-1-associated phosphatase action on CD3-zeta context retains plasma-membrane CD3G.
Reason: This source row asserts compartment membership of the receptor-containing assembly. Human surface and structural evidence supports that compartment; the event does not make CD3G the kinase, phosphatase, ligand-binding TCR chain or the other protein named in its title.
Supporting Evidence:
Reactome:R-HSA-389758
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-8850326
ACCEPT
Summary: The Reactome CD1-presented self-lipid recognition context retains plasma-membrane CD3G.
Reason: This source row asserts compartment membership of the receptor-containing assembly. Human surface and structural evidence supports that compartment; the event does not make CD3G the kinase, phosphatase, ligand-binding TCR chain or the other protein named in its title.
Supporting Evidence:
Reactome:R-HSA-8850326
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-8850356
ACCEPT
Summary: The Reactome CD1-presented microbial-lipid recognition context retains plasma-membrane CD3G.
Reason: This source row asserts compartment membership of the receptor-containing assembly. Human surface and structural evidence supports that compartment; the event does not make CD3G the kinase, phosphatase, ligand-binding TCR chain or the other protein named in its title.
Supporting Evidence:
Reactome:R-HSA-8850356
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-8852200
ACCEPT
Summary: The Reactome PTPN22-dependent LCK inactivation context retains plasma-membrane CD3G.
Reason: This source row asserts compartment membership of the receptor-containing assembly. Human surface and structural evidence supports that compartment; the event does not make CD3G the kinase, phosphatase, ligand-binding TCR chain or the other protein named in its title.
Supporting Evidence:
Reactome:R-HSA-8852200
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-8855381
ACCEPT
Summary: The Reactome PTPN22-dependent ZAP70 dephosphorylation context retains plasma-membrane CD3G.
Reason: This source row asserts compartment membership of the receptor-containing assembly. Human surface and structural evidence supports that compartment; the event does not make CD3G the kinase, phosphatase, ligand-binding TCR chain or the other protein named in its title.
Supporting Evidence:
Reactome:R-HSA-8855381
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-8866277
ACCEPT
Summary: CD3G is a membrane cargo component in the AP-2 cargo binding context.
Reason: The Reactome endocytic context is compatible with a surface TCR entering coated pits. It does not assign the named coat-remodeling or catalytic step to CD3G. Its sorting tail and human internalization data independently support the membrane itinerary.
Supporting Evidence:
Reactome:R-HSA-8866277
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-8867754
ACCEPT
Summary: CD3G is a membrane cargo component in the BAR-protein recruitment context.
Reason: The Reactome endocytic context is compatible with a surface TCR entering coated pits. It does not assign the named coat-remodeling or catalytic step to CD3G. Its sorting tail and human internalization data independently support the membrane itinerary.
Supporting Evidence:
Reactome:R-HSA-8867754
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-8867756
ACCEPT
Summary: CD3G is a membrane cargo component in the cargo/CLASP recruitment context.
Reason: The Reactome endocytic context is compatible with a surface TCR entering coated pits. It does not assign the named coat-remodeling or catalytic step to CD3G. Its sorting tail and human internalization data independently support the membrane itinerary.
Supporting Evidence:
Reactome:R-HSA-8867756
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-8868071
ACCEPT
Summary: CD3G is a membrane cargo component in the PIK3C2A recruitment context.
Reason: The Reactome endocytic context is compatible with a surface TCR entering coated pits. It does not assign the named coat-remodeling or catalytic step to CD3G. Its sorting tail and human internalization data independently support the membrane itinerary.
Supporting Evidence:
Reactome:R-HSA-8868071
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-8868072
ACCEPT
Summary: CD3G is a membrane cargo component in the phosphoinositide phosphorylation context.
Reason: The Reactome endocytic context is compatible with a surface TCR entering coated pits. It does not assign the named coat-remodeling or catalytic step to CD3G. Its sorting tail and human internalization data independently support the membrane itinerary.
Supporting Evidence:
Reactome:R-HSA-8868072
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-8868230
ACCEPT
Summary: CD3G is a membrane cargo component in the SNX9-associated actin machinery recruitment context.
Reason: The Reactome endocytic context is compatible with a surface TCR entering coated pits. It does not assign the named coat-remodeling or catalytic step to CD3G. Its sorting tail and human internalization data independently support the membrane itinerary.
Supporting Evidence:
Reactome:R-HSA-8868230
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-8868236
ACCEPT
Summary: CD3G is a membrane cargo component in the dynamin recruitment context.
Reason: The Reactome endocytic context is compatible with a surface TCR entering coated pits. It does not assign the named coat-remodeling or catalytic step to CD3G. Its sorting tail and human internalization data independently support the membrane itinerary.
Supporting Evidence:
Reactome:R-HSA-8868236
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-8868648
ACCEPT
Summary: CD3G is a membrane cargo component in the synaptojanin-dependent lipid hydrolysis context.
Reason: The Reactome endocytic context is compatible with a surface TCR entering coated pits. It does not assign the named coat-remodeling or catalytic step to CD3G. Its sorting tail and human internalization data independently support the membrane itinerary.
Supporting Evidence:
Reactome:R-HSA-8868648
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-8868651
ACCEPT
Summary: CD3G is a membrane cargo component in the endophilin-synaptojanin recruitment context.
Reason: The Reactome endocytic context is compatible with a surface TCR entering coated pits. It does not assign the named coat-remodeling or catalytic step to CD3G. Its sorting tail and human internalization data independently support the membrane itinerary.
Supporting Evidence:
Reactome:R-HSA-8868651
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-8868661
ACCEPT
Summary: CD3G is a membrane cargo component in the dynamin-mediated vesicle scission context.
Reason: The Reactome endocytic context is compatible with a surface TCR entering coated pits. It does not assign the named coat-remodeling or catalytic step to CD3G. Its sorting tail and human internalization data independently support the membrane itinerary.
Supporting Evidence:
Reactome:R-HSA-8868661
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-9664261
ACCEPT
Summary: The plasma-membrane assertion is retained; the SYK phosphorylation in a Leishmania-associated receptor complex context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-9664261
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-9664268
ACCEPT
Summary: The plasma-membrane assertion is retained; the opsonized Leishmania recognition context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-9664268
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-9664270
ACCEPT
Summary: The plasma-membrane assertion is retained; the FCGR3A-associated PLCG recruitment context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-9664270
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-9664271
ACCEPT
Summary: The plasma-membrane assertion is retained; the PLCG release from FCGR3A context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-9664271
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-9664273
ACCEPT
Summary: The plasma-membrane assertion is retained; the SYK recruitment to a pathogen-associated receptor context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-9664273
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-9664275
ACCEPT
Summary: The plasma-membrane assertion is retained; the phosphorylation of receptor-associated signaling dimers context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-9664275
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-9664278
ACCEPT
Summary: The plasma-membrane assertion is retained; the PLCG activation downstream of FCGR3A context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-9664278
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-9664406
ACCEPT
Summary: The plasma-membrane assertion is retained; the IgG-pathogen binding to FCGR3A context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-9664406
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-9666425
ACCEPT
Summary: The plasma-membrane assertion is retained; the VAV phosphorylation context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-9666425
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-9666426
ACCEPT
Summary: The plasma-membrane assertion is retained; the CRKII-DOCK180-ELMO binding context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-9666426
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-9666428
ACCEPT
Summary: The plasma-membrane assertion is retained; the DOCK180-mediated nucleotide exchange context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-9666428
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-9666430
ACCEPT
Summary: The plasma-membrane assertion is retained; the VAV-mediated nucleotide exchange context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-9666430
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-9666435
ACCEPT
Summary: The plasma-membrane assertion is retained; the VAV recruitment to SYK context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-9666435
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-9666458
ACCEPT
Summary: The plasma-membrane assertion is retained; the receptor movement toward the parasitophorous vacuole context is bounded.
Reason: Independent human TCR evidence establishes CD3G at the plasma membrane. The source Fc-receptor/CD3-dimer context does not independently resolve a CD3G-specific molecular role, and is not used to infer phagocytosis or enzyme activity. Preserve the location and original source while keeping that pathway attribution separate.
Supporting Evidence:
Reactome:R-HSA-9666458
GO:0007163 establishment or maintenance of cell polarity
IMP
PMID:12407027
Contribution of CD3 gamma to TCR regulation and signaling in...
KEEP AS NON CORE
Summary: CD3G deficiency perturbs polarization of activated human T cells.
Reason: The complete source abstract explicitly reports defective adhesion and polarization on ICAM1-coated dishes in human CD3G-deficient cells. Retain this cellular consequence outside the molecular core; it does not show that CD3G directly reorganizes actin or binds ICAM1.
Supporting Evidence:
GO:0007166 cell surface receptor signaling pathway
IBA
GO_REF:0000033
ACCEPT
Summary: Inherited cell-surface receptor signaling is consistent with the CD3G ITAM role.
Reason: This PAINT assertion is retained as curated inheritance with independent human target support. The original IBD node was not reconstructed and the target appearing among descendant evidence is not circularity.
Supporting Evidence:
GO_REF:0000033
GO:0007166 cell surface receptor signaling pathway
IC
PMID:9485181
Assembly of the TCR/CD3 complex: CD3 epsilon/delta and CD3 e...
ACCEPT
Summary: TCR complex membership supports CD3G participation in receptor signaling.
Reason: The IC inference is consistent with human receptor assembly and CD3G-tail effector binding; it does not attribute a catalytic kinase activity to CD3G.
Supporting Evidence:
GO:0007166 cell surface receptor signaling pathway
IEA
GO_REF:0000002
ACCEPT
Summary: The electronic CD3-family signaling association is biologically supported.
Reason: The target ITAM supplies phosphorylation-dependent effector docking within the membrane receptor. That target evidence corroborates the domain-derived process assignment.
Supporting Evidence:
GO_REF:0000002
GO:0007166 cell surface receptor signaling pathway
IMP
PMID:12407027
Contribution of CD3 gamma to TCR regulation and signaling in...
ACCEPT
Summary: Human CD3G contributes to selected mature-T-cell signaling responses.
Reason: The source abstract reports that several responses remain normal or nearly normal while adhesion/polarization and activation-induced death differ. Retain participation without claiming universal loss of TCR signaling after CD3G deficiency.
Supporting Evidence:
GO:0009897 external side of plasma membrane
IBA
GO_REF:0000033
ACCEPT
Summary: The CD3G extracellular domain lies on the external face of the plasma membrane.
Reason: The inherited location agrees with the reviewed type-I topology and the human extracellular CD3 gamma-epsilon structure. The PAINT IBD itself was not inspected; its short source list is not a reason to reject the compatible location.
Supporting Evidence:
GO_REF:0000033
GO:0015031 protein transport
IMP
PMID:12794121
TCR dynamics in human mature T lymphocytes lacking CD3 gamma...
MODIFY
Summary: CD3G supports receptor internalization through its cytoplasmic sorting tail.
Reason: Human deficiency slows early ligand-induced uptake, while constitutive internalization and degradation remain largely preserved. The tail motif supplies sorting-adaptor recognition, established separately by mutational and peptide-binding work; this is physical participation rather than necessity alone. Refine the broad transport assertion to receptor internalization, without claiming CD3G itself catalyzes vesicle scission.
Proposed replacements: receptor internalization
Supporting Evidence:
PMID:12794121
early ligand-induced endocytosis was impaired
GO:0016020 membrane
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: The broad membrane term is correct but less informative than the established plasma-membrane role.
Reason: The InterPro mapping agrees with single-pass topology. Retain this broad compartment as non-core; the specific plasma-membrane and TCR-complex locations are already represented.
Supporting Evidence:
GO_REF:0000002
GO:0030159 signaling receptor complex adaptor activity
NAS
PMID:12794121
TCR dynamics in human mature T lymphocytes lacking CD3 gamma...
ACCEPT
Summary: CD3G physically supports the assembly and signaling capacity of the TCR complex.
Reason: The human deficiency study supports this adaptor role, with independent mutational assembly, extracellular interface and ITAM-effector evidence. CD3G contributes contacts and a docking tail; it is not merely a downstream response marker.
GO:0030669 clathrin-coated endocytic vesicle membrane
TAS
Reactome:R-HSA-8868658
KEEP AS NON CORE
Summary: CD3G can occupy the coated-vesicle membrane during HSPA8-mediated uncoating.
Reason: Retain the Reactome cargo-location annotation as a trafficking context. The sorting tail helps recruit the endocytic apparatus, but CD3G is not thereby the coat, chaperone, phosphatase or GTPase executing this event.
Supporting Evidence:
Reactome:R-HSA-8868658
GO:0030669 clathrin-coated endocytic vesicle membrane
TAS
Reactome:R-HSA-8868659
KEEP AS NON CORE
Summary: CD3G can occupy the coated-vesicle membrane during auxilin recruitment.
Reason: Retain the Reactome cargo-location annotation as a trafficking context. The sorting tail helps recruit the endocytic apparatus, but CD3G is not thereby the coat, chaperone, phosphatase or GTPase executing this event.
Supporting Evidence:
Reactome:R-HSA-8868659
GO:0030669 clathrin-coated endocytic vesicle membrane
TAS
Reactome:R-HSA-8868660
KEEP AS NON CORE
Summary: CD3G can occupy the coated-vesicle membrane during HSPA8 recruitment.
Reason: Retain the Reactome cargo-location annotation as a trafficking context. The sorting tail helps recruit the endocytic apparatus, but CD3G is not thereby the coat, chaperone, phosphatase or GTPase executing this event.
Supporting Evidence:
Reactome:R-HSA-8868660
GO:0030669 clathrin-coated endocytic vesicle membrane
TAS
Reactome:R-HSA-8868661
KEEP AS NON CORE
Summary: CD3G can occupy the coated-vesicle membrane during dynamin-dependent scission.
Reason: Retain the Reactome cargo-location annotation as a trafficking context. The sorting tail helps recruit the endocytic apparatus, but CD3G is not thereby the coat, chaperone, phosphatase or GTPase executing this event.
Supporting Evidence:
Reactome:R-HSA-8868661
GO:0030669 clathrin-coated endocytic vesicle membrane
TAS
Reactome:R-HSA-8869438
KEEP AS NON CORE
Summary: CD3G can occupy the coated-vesicle membrane during coat-associated protein dissociation.
Reason: Retain the Reactome cargo-location annotation as a trafficking context. The sorting tail helps recruit the endocytic apparatus, but CD3G is not thereby the coat, chaperone, phosphatase or GTPase executing this event.
Supporting Evidence:
Reactome:R-HSA-8869438
GO:0030669 clathrin-coated endocytic vesicle membrane
TAS
Reactome:R-HSA-8871193
KEEP AS NON CORE
Summary: CD3G can occupy the coated-vesicle membrane during AAK1 dissociation/AP-2 dephosphorylation.
Reason: Retain the Reactome cargo-location annotation as a trafficking context. The sorting tail helps recruit the endocytic apparatus, but CD3G is not thereby the coat, chaperone, phosphatase or GTPase executing this event.
Supporting Evidence:
Reactome:R-HSA-8871193
GO:0030669 clathrin-coated endocytic vesicle membrane
TAS
Reactome:R-HSA-8871194
KEEP AS NON CORE
Summary: CD3G can occupy the coated-vesicle membrane during RAB5/GAPVD1 association.
Reason: Retain the Reactome cargo-location annotation as a trafficking context. The sorting tail helps recruit the endocytic apparatus, but CD3G is not thereby the coat, chaperone, phosphatase or GTPase executing this event.
Supporting Evidence:
Reactome:R-HSA-8871194
GO:0032395 MHC class II receptor activity
IDA
PMID:1323144
Activation-induced ubiquitination of the T cell antigen rece...
ACCEPT
Summary: CD3G contributes to the activity of an appropriately MHC-II-restricted TCR complex.
Reason: The preserved contributes_to qualifier makes this a complex-level claim, not direct MHC-II binding by CD3G. Eleven inspected human production GO-CAM activities include P09693 in the alpha-beta TCR complex enabling this activity, using shared PMID:1323144/PMID:31461748 provenance. The original paper cache alone does not reveal the clone-specific gamma assay; the positive curated complex model and human composition evidence are distinguished from a new verification of that experiment.
Supporting Evidence:
GO:0042105 alpha-beta T cell receptor complex
IBA
GO_REF:0000033
ACCEPT
Summary: CD3G is a conserved component of the alpha-beta TCR complex.
Reason: Retain the curated PAINT inference, directly corroborated by human structural composition. The underlying ancestral placement remains uninspected rather than being reconstructed from the donor list.
Supporting Evidence:
GO_REF:0000033
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: Human CD3 gamma-epsilon dimers associate within the alpha-beta receptor complex.
Reason: The cited human association study supports membership. Its historical double-receptor interpretation is superseded for the described human structural assembly by the later one-alpha-beta-pair complex.
Supporting Evidence:
GO:0042105 alpha-beta T cell receptor complex
IEA
GO_REF:0000120
ACCEPT
Summary: The combined electronic assignment to the alpha-beta TCR complex is independently supported.
Reason: Preserve the ARBA and mouse orthology source entities. The actual human complex structure confirms CD3G membership without requiring an uninspected rule or donor assay to carry the conclusion.
Supporting Evidence:
GO_REF:0000120
GO:0042105 alpha-beta T cell receptor complex
IPI
PMID:31461748
Structural basis of assembly of the human T cell receptor-CD...
ACCEPT
Summary: The human structural complex contains one CD3 gamma-epsilon pair.
Reason: The cryo-EM assembly establishes direct physical membership in the alpha-beta receptor complex, rather than merely a deficiency phenotype.
Supporting Evidence:
GO:0042106 gamma-delta T cell receptor complex
NAS
PMID:16418397
Stoichiometry of the murine gammadelta T cell receptor.
ACCEPT
Summary: CD3G is also a component of human gamma-delta TCR complexes.
Reason: The original NAS source measures murine stoichiometry; independent 2024 human structures establish gamma-epsilon membership. Their inclusion of delta-epsilon is kept separate from the older mouse architecture.
Supporting Evidence:
GO:0042110 T cell activation
NAS
PMID:12407027
Contribution of CD3 gamma to TCR regulation and signaling in...
ACCEPT
Summary: CD3G contributes to T cell activation through the TCR-CD3 receptor.
Reason: The human study reports specialized activation responses despite residual signaling. Retain the broad activation process without treating CD3G as independently sufficient to activate a T cell.
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: The TCR association is retained, with the original letter-specific evidence unresolved.
Reason: The cached PMID:11186279 letter contains no scientific abstract or accessible assay description. Independent human CD3G mutational and receptor-structure evidence establishes the same TCR association; this supports qualified non-core binding without asserting that the original letter directly measured it.
GO:0042802 identical protein binding
IDA
PMID:14967045
Homooligomerization of the cytoplasmic domain of the T cell ...
KEEP AS NON CORE
Summary: The isolated CD3G cytoplasmic domain oligomerizes in solution.
Reason: The complete abstract explicitly includes CD3 gamma among the recombinant cytoplasmic ITAM domains. Retain that in-vitro binding observation without converting it into a native full-length CD3G homodimer or a second physiological receptor architecture.
Supporting Evidence:
GO:0045059 positive thymic T cell selection
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: CD3G contributes to thymic selection in the context of receptor signaling.
Reason: The curated phylogenetic assertion is compatible with TCR-dependent selection and human repertoire abnormalities. Keep the developmental outcome outside the molecular core. The original PAINT IBD and its complete donor experiments were not independently reconstructed.
Supporting Evidence:
GO_REF:0000033
GO:0046629 gamma-delta T cell activation
NAS
PMID:30976362
T cell receptor signaling for Ξ³Ξ΄T cell development.
ACCEPT
Summary: The CD3G signaling module participates in gamma-delta T cell activation.
Reason: The cited review and independent human reconstituted receptor/activation evidence support the conserved signaling role. This does not mean that CD3G determines gamma-delta antigen specificity.
Supporting Evidence:
GO:0046631 alpha-beta T cell activation
NAS
PMID:29789755
Regulatory mechanisms in T cell receptor signalling.
ACCEPT
Summary: The CD3G signaling module participates in alpha-beta T cell activation.
Reason: The review attribution agrees with target human receptor assembly and deficiency evidence. CD3G supports the receptor signal rather than recognizing peptide-MHC independently.
GO:0050852 T cell receptor signaling pathway
IDA
PMID:1323144
Activation-induced ubiquitination of the T cell antigen rece...
ACCEPT
Summary: CD3G participates in TCR signaling as a receptor subunit with an ITAM.
Reason: The original ubiquitination abstract names zeta and delta, so it is not quoted as a gamma-specific ubiquitination assay. Human CD3G-tail binding and deficiency evidence independently support the signaling process; the original source-specific assay remains unverified.
GO:0050852 T cell receptor signaling pathway
NAS
PMID:29789755
Regulatory mechanisms in T cell receptor signalling.
ACCEPT
Summary: CD3G contributes to TCR signal transmission in adaptive T cells.
Reason: This author-statement review is consistent with the independently established human receptor-adaptor and ITAM roles.
GO:0050852 T cell receptor signaling pathway
NAS
PMID:30976362
T cell receptor signaling for Ξ³Ξ΄T cell development.
ACCEPT
Summary: CD3G supports gamma-delta TCR signal transmission.
Reason: The review attribution is consistent with human receptor composition and functional reconstitution; species-specific stoichiometry is not collapsed.
Supporting Evidence:
GO:0065003 protein-containing complex assembly
NAS
PMID:12794121
TCR dynamics in human mature T lymphocytes lacking CD3 gamma...
ACCEPT
Summary: CD3G makes physical contacts that support assembly of the receptor complex.
Reason: Human site-directed mutagenesis and structural interfaces identify work done by CD3G in assembly. Residual surface receptors in deficient mature T cells do not erase that contribution, but rule out an absolute requirement in every setting.
GO:0070228 regulation of lymphocyte apoptotic process
IMP
PMID:12407027
Contribution of CD3 gamma to TCR regulation and signaling in...
KEEP AS NON CORE
Summary: CD3G deficiency alters activation-induced death in human T cells.
Reason: The source abstract directly reports increased activation-induced cell death. Retain the downstream cellular outcome as non-core without assigning intrinsic apoptosis-enzyme activity or a universal death phenotype to CD3G.
Supporting Evidence:
GO:0035612 AP-2 adaptor complex binding
IPI
PMID:9230070
Regulation and function of the CD3gamma DxxxLL motif: a bind...
NEW
Summary: The CD3 gamma cytoplasmic DxxxLL motif associates with AP-2 adaptor complexes.
Reason: PMID:9230070 recovered AP-2 adaptins from human Jurkat cytosol with immobilized human CD3 gamma tail peptides. Replacing the dileucines with alanines abolished alpha- and beta- adaptin recovery; D127 substitution and altered D-to-LL spacing reduced binding. This supports motif-dependent AP-2 complex association with IPI evidence, without a purified binary interaction or identification of the contacting subunit; the authors could not exclude mediation by another molecule. PMID:8187769 independently links the CD3 gamma dileucine motif to PKC-induced down-regulation of the intact receptor in human JGN transfectants, providing functional context rather than a second AP-2-binding assay. AP-1 was also captured in the peptide assay. AP-2 is selected for the surface-receptor internalization role; AP-1 motif recognition is acknowledged without asserting an additional TGN-trafficking function.
Supporting Evidence:
PMID:9230070
the CD3gamma D127xxxLL131/132 sequence represents one united motif for binding of both AP-1 and AP-2

Core Functions

CD3 gamma supplies receptor-assembly contacts in the gamma-epsilon module and a cytoplasmic ITAM that recruits signaling effectors after phosphorylation. These activities couple an assembled membrane TCR to intracellular signaling; antigen specificity belongs to the clonotypic receptor chains.

Supporting Evidence:

The cytoplasmic dileucine sorting signal binds AP-2 and helps couple the surface TCR to internalization. Phosphoserine-dependent exposure and the surrounding tail context regulate this interaction in the intact receptor; uptake remains possible through other routes.

Supporting Evidence:

References

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Suggested Questions for Experts

Q: How much do CD3G-dependent assembly, ITAM signaling and regulated trafficking separately explain the variable immunodeficiency and regulatory-T-cell phenotypes in patients?

Q: How closely do the CD3 dimer composition and stoichiometry of endogenous human gamma-delta TCR subsets match the reconstituted Vgamma9Vdelta2 and Vgamma5Vdelta1 structures?

Q: Should the preserved enables qualifiers on the four transmembrane signaling receptor activity annotations be curated as contributes_to for CD3 gamma, given its assembly and ITAM signaling role within the antigen-recognizing TCR complex?

Suggested Experiments

Experiment: Compare wild-type CD3G with separate ITAM, phosphoserine and dileucine-motif mutants in a matched human T-cell background, measuring receptor assembly, surface abundance, ligand-triggered internalization and recycling alongside signaling. Report precursor versus mature-chain numbering and receptor-expression controls.

Deep Research

Falcon

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πŸ“š Additional Documentation

Notes

(CD3G-notes.md)

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