CD3D

Summary: CD3D participates in adaptive immunity through the TCR signaling apparatus.

Reason: The NAS source is a signaling review whose complete available abstract was read. Adaptive immunity is a valid broad context; T cell receptor signaling is the more informative direct process. No additional immune effector mechanism is inferred.

Summary: The broad immune-system annotation is compatible with the established TCR role.

Reason: The ARBA source is preserved. Target structural and signaling evidence support the general biological context, while the individual ARBA rule was not reconstructed.

Summary: CD3D contributes to the transmembrane signaling activity of the assembled TCR complex.

Reason: The PAINT assertion describes inherited function and agrees with target receptor assembly and signaling evidence. The source enables qualifier is preserved; the biological interpretation is a subunit contribution, not independent peptide-MHC recognition. The original IBD tree and alignment were not reconstructed, and target self-reference is legitimate descendant support.

Summary: Complex membership supports the curator-inferred receptor activity.

Reason: The original abstract establishes CD3 delta-epsilon assembly with TCR chains, corroborated by the modern human structure. Its historical double-TCR-heterodimer model is not required for this inference and is not adopted. Receptor activity is interpreted at the assembled-complex level.

Summary: The ITAM-associated receptor-function mapping agrees with the target biology.

Reason: The InterPro mapping is preserved and is supported independently by CD3D membrane topology, receptor assembly and its ITAM-bearing tail. No autonomous ligand recognition or enzymatic catalysis is assigned.

Summary: The experimentally curated SGTB association is retained as non-core binding.

Reason: The HuRI source row identifies SGTB/Q96EQ0, and the reviewed UniProt CD3D interaction record corroborates that exact pair. Selected general HuRI Methods were read, but the original target supplementary entry was not independently inspected. Retain the supported qualitative interaction under the project instruction; no co-chaperone function, physiological requirement or more specific molecular activity is inferred.

Summary: Human fetal-liver clones expressed intracellular CD3 delta without surface CD3.

Reason: The complete abstract identifies fetal-liver clones FL121/125 with cytoplasmic CD3 delta/epsilon and negative adult peripheral-blood CD3-negative NK controls. It supports intracellular localization, not a resolved ER or Golgi compartment, nor a soluble cytosolic topology. Preserve the broad NAS as a contextual location.

Summary: Human Jurkat surface measurements support plasma-membrane TCR-CD3 localization.

Reason: The inspected primary Results and Methods distinguish anti-TCR alpha-beta and OKT3 surface measurements, vector controls, and unchanged CD28/HLA class I controls. This supports the receptor-complex location. The separate TRIM coimmunoprecipitation experiment did not detect CD3 delta and is not misrepresented as direct TRIM-CD3D binding.

Summary: The human receptor structure places CD3 delta in its membrane-spanning assembly.

Reason: The complete abstract and accessible publisher structural preview resolve extracellular domains and transmembrane helices in the TCR-CD3 octamer. This supports the membrane context; it is not an intact-cell localization assay or a complete structure of the cytoplasmic ITAM tails.

Summary: The UniProt location mapping agrees with plasma-membrane receptor assembly.

Reason: The controlled-vocabulary mapping is independently supported by the human receptor structure and surface measurements. The exact source mapping is retained.

Summary: The Reactome:R-HSA-198955 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-202165 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-202168 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-202174 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-202214 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-202216 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-202233 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-202245 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-202248 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-202291 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-202307 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-202344 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-389758 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-8850326 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-8850356 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-8852200 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-8855381 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-8866277 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-8867754 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-8867756 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-8868071 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-8868072 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-8868230 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-8868236 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-8868648 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-8868651 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The Reactome:R-HSA-8868661 location assertion places receptor-associated CD3D at the plasma membrane.

Reason: The cached reaction summary and exact GOA location were read. This is a location of the TCR-associated component within a curated reaction context, independently corroborated by human TCR structure and surface measurements. It does not assign the reaction enzyme, lipid-binding specificity, phosphatase activity, or endocytic machinery function to CD3D.

Summary: The inherited cell-surface signaling process is consistent with TCR signaling.

Reason: CD3D supplies a signaling and assembly interface in a cell-surface receptor. The broad parent process is valid alongside the source-specific TCR process. No original PAINT node placement or loss analysis was independently reconstructed.

Summary: The complex-membership inference supports cell-surface receptor signaling.

Reason: The source demonstrates TCR/CD3 association, and modern structure independently confirms the relevant assembly. The historical double-heterodimer stoichiometry is not adopted; the inference only requires participation in the signaling receptor.

Summary: The ITAM-domain process mapping agrees with the established signaling role.

Reason: The broad electronic process is corroborated by the target ITAM-containing receptor subunit. It does not imply that an isolated ITAM alone constitutes an autonomous receptor.

Summary: CD3 delta has an extracellular domain on the external face of the plasma membrane.

Reason: The PAINT location is corroborated by reviewed type I topology and the extracellular CD3 delta-epsilon assembly in the human structure. The assertion does not locate the cytoplasmic tail outside the cell.

Summary: The membrane assertion can be specified as plasma membrane.

Reason: The electronic source is broad, while target receptor structure and human surface measurements establish the plasma-membrane location. The original GOA identifier is preserved and the refinement is recorded separately.

Proposed replacements: plasma membrane

Summary: The Reactome:R-HSA-8868658 assertion records receptor cargo in an endocytic vesicle membrane.

Reason: The curated location is compatible with trafficking of the TCR-CD3 complex. CD3D is retained as cargo in this context, not assigned clathrin uncoating, scission, ATPase or GTPase activity. The CD3 gamma dileucine sorting motif is not transferred to CD3 delta. The cached reaction summary does not by itself establish a CD3D-specific endocytic mechanism.

Summary: The Reactome:R-HSA-8868659 assertion records receptor cargo in an endocytic vesicle membrane.

Reason: The curated location is compatible with trafficking of the TCR-CD3 complex. CD3D is retained as cargo in this context, not assigned clathrin uncoating, scission, ATPase or GTPase activity. The CD3 gamma dileucine sorting motif is not transferred to CD3 delta. The cached reaction summary does not by itself establish a CD3D-specific endocytic mechanism.

Summary: The Reactome:R-HSA-8868660 assertion records receptor cargo in an endocytic vesicle membrane.

Reason: The curated location is compatible with trafficking of the TCR-CD3 complex. CD3D is retained as cargo in this context, not assigned clathrin uncoating, scission, ATPase or GTPase activity. The CD3 gamma dileucine sorting motif is not transferred to CD3 delta. The cached reaction summary does not by itself establish a CD3D-specific endocytic mechanism.

Summary: The Reactome:R-HSA-8868661 assertion records receptor cargo in an endocytic vesicle membrane.

Reason: The curated location is compatible with trafficking of the TCR-CD3 complex. CD3D is retained as cargo in this context, not assigned clathrin uncoating, scission, ATPase or GTPase activity. The CD3 gamma dileucine sorting motif is not transferred to CD3 delta. The cached reaction summary does not by itself establish a CD3D-specific endocytic mechanism.

Summary: The Reactome:R-HSA-8869438 assertion records receptor cargo in an endocytic vesicle membrane.

Reason: The curated location is compatible with trafficking of the TCR-CD3 complex. CD3D is retained as cargo in this context, not assigned clathrin uncoating, scission, ATPase or GTPase activity. The CD3 gamma dileucine sorting motif is not transferred to CD3 delta. The cached reaction summary does not by itself establish a CD3D-specific endocytic mechanism.

Summary: The Reactome:R-HSA-8871193 assertion records receptor cargo in an endocytic vesicle membrane.

Reason: The curated location is compatible with trafficking of the TCR-CD3 complex. CD3D is retained as cargo in this context, not assigned clathrin uncoating, scission, ATPase or GTPase activity. The CD3 gamma dileucine sorting motif is not transferred to CD3 delta. The cached reaction summary does not by itself establish a CD3D-specific endocytic mechanism.

Summary: The Reactome:R-HSA-8871194 assertion records receptor cargo in an endocytic vesicle membrane.

Reason: The curated location is compatible with trafficking of the TCR-CD3 complex. CD3D is retained as cargo in this context, not assigned clathrin uncoating, scission, ATPase or GTPase activity. The CD3 gamma dileucine sorting motif is not transferred to CD3 delta. The cached reaction summary does not by itself establish a CD3D-specific endocytic mechanism.

Summary: CD3D contributes to MHC class II receptor activity within an appropriate alpha-beta TCR complex.

Reason: The contributes_to qualifier explicitly allows a necessary signaling subunit of a complex to contribute without directly contacting MHC. The actual production GO-CAM 685de18700003492/685de18700003493 assigns this activity to GO:0042105 and includes P04234 as a subunit, citing 1323144 for activity and 31461748 for composition. The original 1992 cache is abstract-only, so no independent reconstruction of its clone or class restriction is claimed. Retain curator-intended complex-level scope; CD3D is not exclusively class-II-specific.

Summary: CD3 delta is a component of the T cell receptor complex.

Reason: The original comparative ZAP70/Syk abstract was read, but its complete CD3D-specific experimental panel was not recovered. Defer to the curated complex assertion, independently corroborated by the modern human alpha-beta structure and human gamma-delta structures.

Summary: The PAINT inherited component supports alpha-beta TCR-complex membership.

Reason: CD3 delta-epsilon is a directly resolved subcomplex of the human octamer, with one TCR alpha-beta pair and three CD3 dimers. The CD3 signaling unit alone is a hexamer; the complete receptor contains eight chains. The historical 1998 double-TCR model and uninspected automated rule details are not used as modern stoichiometric evidence.

Summary: The original experimental association supports alpha-beta TCR-complex membership.

Reason: CD3 delta-epsilon is a directly resolved subcomplex of the human octamer, with one TCR alpha-beta pair and three CD3 dimers. The CD3 signaling unit alone is a hexamer; the complete receptor contains eight chains. The historical 1998 double-TCR model and uninspected automated rule details are not used as modern stoichiometric evidence.

Summary: The combined electronic component supports alpha-beta TCR-complex membership.

Reason: CD3 delta-epsilon is a directly resolved subcomplex of the human octamer, with one TCR alpha-beta pair and three CD3 dimers. The CD3 signaling unit alone is a hexamer; the complete receptor contains eight chains. The historical 1998 double-TCR model and uninspected automated rule details are not used as modern stoichiometric evidence.

Summary: The human cryo-EM assembly supports alpha-beta TCR-complex membership.

Reason: CD3 delta-epsilon is a directly resolved subcomplex of the human octamer, with one TCR alpha-beta pair and three CD3 dimers. The CD3 signaling unit alone is a hexamer; the complete receptor contains eight chains. The historical 1998 double-TCR model and uninspected automated rule details are not used as modern stoichiometric evidence.

Summary: Isolated recombinant CD3 delta cytoplasmic domains oligomerize in vitro.

Reason: The complete available abstract explicitly includes CD3 delta among the tested oligomeric domains. This supports the bounded biochemical observation; the absence of a demonstrated physiological homomer does not refute it. The cited numerical dissociation constants belong to zeta, not delta. Retain non-core binding without asserting a full-length CD3D homomer or an invariant native stoichiometry.

Summary: The PAINT inherited-process assertion is retained in its developmental context.

Reason: The reviewed UniProt record and established TCR signaling role support participation in positive selection. CD3D performs signaling/assembly work rather than merely being consumed by the process. The precise original mouse selection experiments were not reread, so no newly verified arrest stage or direct CD4/CD8 interface is asserted. This contextual developmental process is not a separate core molecular activity.

Summary: The Ensembl Compara mouse-ortholog transfer is retained in its developmental context.

Reason: The reviewed UniProt record and established TCR signaling role support participation in positive selection. CD3D performs signaling/assembly work rather than merely being consumed by the process. The precise original mouse selection experiments were not reread, so no newly verified arrest stage or direct CD4/CD8 interface is asserted. This contextual developmental process is not a separate core molecular activity.

Summary: The manual mouse-ortholog transfer is retained in its developmental context.

Reason: The reviewed UniProt record and established TCR signaling role support participation in positive selection. CD3D performs signaling/assembly work rather than merely being consumed by the process. The precise original mouse selection experiments were not reread, so no newly verified arrest stage or direct CD4/CD8 interface is asserted. This contextual developmental process is not a separate core molecular activity.

Summary: CD3D contributes to alpha-beta T cell activation through receptor signaling.

Reason: The source review provides broad signaling context, and the molecular assembly establishes CD3D as a signaling subunit. Retain the wider cellular process as non-core without assigning every downstream effector response to CD3D.

Summary: CD3 delta participates in the TCR signaling apparatus and is modified following receptor activation.

Reason: The original abstract directly reports activation-dependent ubiquitination of CD3 delta. That modification alone is not treated as proof of catalysis or of being the entity performing ubiquitination. Independent ITAM and receptor-assembly evidence establish CD3D structural/signaling participation in the TCR pathway.

Summary: T cell receptor signaling is the direct process served by CD3D.

Reason: The review source is abstract-only and supplies broad pathway context. Target structure and the curated CD3 ITAM signaling reaction independently support CD3D participation; this is not a claim that the review performed a new target assay.

Summary: CD3 delta supplies physical support for assembly of the multiprotein TCR signaling receptor.

Reason: Retain this historical proposal: CD3 delta itself supplies extracellular packing and a transmembrane assembly interface, satisfying the adaptor definition by physical work rather than necessity alone. Exact signed-main GOA independently confirms same-role human CD3E and CD3G annotations to this term. No additional process term or ancestor/descendant adaptor proposal is introduced.

Summary: Human CD3 delta is a subunit of the gamma-delta TCR-CD3 complex in primary and cultured human gamma-delta T cells.

Reason: Resolves issue #4221. Human CD3E, CD3G, CD247, TRDC and TRGC1/2 carry GO:0042106 only by NAS from PMID:16418397, a murine stoichiometry study; the absence of CD3D matches the murine composition (TCRgammadelta CD3epsilon2 gamma2 zeta2), which does not transfer to human. That same paper leaves the human composition open and reports CD3 delta-epsilon dimers in human gamma-delta TCRs (less than in alpha-beta TCRs on primary cells, comparable on expanded clones (cited therein; the clone comparison as unpublished data)), so this row is consistent with the reference behind the sibling NAS rows. Direct human evidence shows CD3 delta in the receptor: anti-TCRgammadelta immunopurification from healthy-donor PBMCs recovers CD3 delta in roughly equal amounts to the alpha-beta TCR, and native antibody mobility-shift (NAMOS, BN-PAGE) analysis of the cultured gamma-delta clone gammadelta19 gives one CD3 delta and one CD3 gamma per receptor [PMID:17923503]. The 1:1 gamma:delta stoichiometry is therefore established for clones, not for primary cells; membership itself is supported in both. The cryo-EM structure of the human G115 Vgamma9Vdelta2 TCR-CD3 complex resolves CD3 delta [PMID:38657677]. Consistently, CD3 delta deficiency blocks gamma-delta T cell development in humans but not mice [PMID:17923503, citing Dadi et al. 2003]. The comparator check passes: every other human CD3 subunit already carries the term, and the term definition describes the TCR gamma-delta heterodimer as associated with the CD3 complex. This is a cellular-component membership claim supported by biochemistry on primary cells, not necessity-only inference. Mouse Cd3d should not receive this term.