The human P40259 source contains 40 GO assertions, three alternative-product records and 28 original references, supplemented here by five primary references. Original term identifiers, evidence codes, qualifiers, interaction partners and product objects are preserved. The annotation-reviewer and core-function-synthesizer skills were applied with the ClinGen project's standing rule for supported generic protein binding. No NEW annotation is proposed.
This is manual research. A genuine isolated Falcon attempt and its explicit Perplexity-lite fallback failed during network requests and produced no research report. The manually written review and notes are not represented as provider-generated output.
CD79B supplies the Ig-beta chain of the BCR signaling module with CD79A. The human IgM-BCR structure directly establishes its membership alongside membrane immunoglobulin PMID:35981043. Human B-cell experiments demonstrate loss of surface IgM/CD79A after CD79B knockout and stronger recovery with WT CD79B than with G137S PMID:36426942. Selected primary PMC Methods, rescue Results and Figure7 legend were subsequently inspected: sequence-verified WT/G137S human CD79B constructs were transduced into Granta-519 CD79B-knockout clone E4. Flow cytometry and Endo-H/western assays distinguish surface expression and protein maturation, with GFP and mRNA controls. G137S leaves low residual surface expression, so it is not treated as an absolute null in every expression system. The structural source remains abstract-only; atomic contacts and full structural methods were not independently inspected.
The core therefore uses contributes_to_molecular_function for transmembrane signaling receptor activity, in the B-cell receptor complex at the plasma membrane. It does not assert autonomous antigen recognition by CD79B. Original IBA/ISS annotations already use contributes_to; the IEA enables assertion is preserved and interpreted explicitly at the complex-subunit level. The generic immune-system and signaling terms are refined to the existing BCR signaling pathway term. Broad membrane localization is refined to plasma membrane.
The external-side IBA uses is_active_in: the extracellular Ig-alpha/Ig-beta domains contact membrane immunoglobulin and contribute structurally to receptor assembly at that side of the membrane. The separate electronic located_in assertion describes the same extracellular region. They do not place the cytoplasmic ITAM outside the cell. The three source products—Long/P40259-1, Short/P40259-2 and P40259-3—are retained without inferring isoform-exclusive activities from sequence notes alone. B-cell differentiation is a downstream physiological consequence of receptor function and is kept NC.
Four generic binding assertions have exact source-specific IntAct matches:
All four remain KEEP_AS_NON_CORE under the project rule. The database target records were inspected with their participant features; the original complete supplementary constructs and raw assay data were not reanalysed. Multiple assay records from one study and UniProt's interaction listing are not independent biological replications. The canonical caches marked full-text for the 2015 and 2022 variant screens are partial extractions, and are not treated as complete Methods/Results access.
The identical-protein-binding assertion is retained NC because the primary abstract explicitly includes recombinant Ig-beta cytoplasmic domains among oligomerizing ITAM-containing proteins PMID:14967045. This is not equated with a native CD79B homodimer replacing the physiological CD79A–CD79B heterodimer.
The exosome annotation remains NC. The abstract describes B-cell exosome proteomics, and the source-linked Vesiclepedia record specifically identifies human CD79B protein in experiment80 from that study PMID:20458337. The original mass-spectrometry supplement was not independently inspected; the index represents the same evidence, and study-wide western-blot methods do not establish target-specific western validation.
The original Fc-mu-receptor paper's exact CD79B-containing construct was not inspected PMID:36949194. Its IgM-BCR component annotation is retained using the independent human IgM-BCR structure, rather than declaring a wrong-gene citation from the title. Ten cached Reactome summaries support pathway localization; their downstream kinase, phosphatase, lipid-hydrolysis or drug-binding events do not assign those activities to CD79B.
All ten original PMID identifiers and titles were independently checked against official Europe PMC MED metadata; the five added references were checked against official Europe PMC or PubMed records. Existing publication caches were preserved, and missing sources were obtained through the normal fetch commands. PAINT assertions are treated as ancestral-node judgments; donor count and target self-evidence are not grounds for rejection. Short, nonduplicated quotations anchor the core composition, rescue and disease-allele statements. Their aggregate word counts remain within 25 words per source across the review and these notes.
Primary links: human IgM-BCR structure, human surface-expression rescue, mutational interaction screen, cancer neo-interaction screen, cytoplasmic-domain oligomerization.
UniProt P40259 identifies autosomal recessive agammaglobulinemia 6 (AGM6, MIM:612692) and links its G137S variant to the patient study. The primary report identifies a homozygous “glycine to serine at codon 137” [PMID:17675462, https://pubmed.ncbi.nlm.nih.gov/17675462/]. Its journal PDF was independently inspected, including mutation analysis, transfected-cell methods, Results and Figure3/4 legends. The allele is hypomorphic: disulfide-linked CD79A/CD79B assembly is inefficient, and stable Jurkat reconstitution yields reduced surface BCR. The paper also reports that high transient expression can mask the surface-expression defect. The patient phenotype and the biochemical/cellular assays support receptor assembly as the link to impaired B-cell development; neither complete inactivity nor SGTA-dependent disease causation follows. The authentic publication cache remains unchanged and abstract-only.
The 2007 assembly study and the 2022 rescue experiment therefore complement each other while differing in expression system. The latter directly re-tests named G137S in human lymphoma cells, with low surface rescue and immature CD79B protein compared with WT [PMID:36426942, https://pmc.ncbi.nlm.nih.gov/articles/PMC9643646/]. The current developmental annotation remains non-core, now with direct human disease support in addition to the ancestral inference. Mouse deficient-progenitor evidence shows developmental arrest with intact V(D)J recombination; it does not assign CD79B recombinase activity [PMID:12097390, https://pubmed.ncbi.nlm.nih.gov/12097390/; complete abstract inspected].
Ig-beta enhances the speed and extent of Ig-alpha phosphorylation in the experimental receptor system of PMID:8617796 (https://pubmed.ncbi.nlm.nih.gov/8617796/). The complete abstract explicitly describes human PDGFR extracellular/transmembrane domains fused to Ig cytoplasmic tails and expressed in murine A20 IIA1.6 cells. Full Methods and the exact Ig-tail species were not independently resolved. This supports cooperative signaling, without establishing that CD79B directly recruits a particular kinase or protects phosphorylated CD79A from dephosphorylation. Those mechanistic alternatives remain hypotheses.
PMID:9057631 (https://pubmed.ncbi.nlm.nih.gov/9057631/; complete abstract inspected) compares engineered Ig-alpha/Ig-beta heterodimers and homodimers in WEHI-231 cells for apoptosis and associated Syk phosphorylation. It corroborates heterodimer cooperation. Its abstract is not evidence of an internalization assay, and no new apoptosis process assertion is added.
A separate primary source directly addresses trafficking: PMID:10352267 (https://pubmed.ncbi.nlm.nih.gov/10352267/; complete abstract inspected). Single-chain chimeric receptors could internalize, yet failed to reach the MHC class II-enriched compartment efficiently under the conditions tested. The paired chains restored efficient late-endosomal targeting and presentation of temporally restricted antigen. This supports a contextual role for the receptor module in delivery to processing compartments. Full primary Methods and exact construct species were not independently inspected; the claim is not presented as a native human CD79B-only experiment.
No NEW process annotation is proposed. Current QuickGO definitions distinguish movement of activated receptors into the cell (GO:0031623) from expression of antigen in association with MHC at the cell surface (GO:0019882). A receptor being internalized is insufficient by itself to establish participation; an experimentally resolved sorting or adaptor role would be stronger evidence. The accessed chimeric evidence also separates uptake from later antigen trafficking. The question is retained for expert follow-up rather than turned into a direct human GO assertion. The local GO-CAM index had no CD79B/P40259 target entry at review time, which is not evidence that an annotation is missing. No comparator-based gap claim is made.
All rows were reconsidered against the existing source-specific review, UniProt and primary caches. Current generic-binding policy replaces the older explicit NONCORE retention rule; interaction payloads and prior provenance remain intact. Broad membrane is refined to plasma membrane. Extracellular-side rationales now depend on topology and assembly rather than an ordinary relationship qualifier. CD79A multivesicular-body inference is anchored to direct mouse Fig. 5C immunogold (PMID11854359); CD79B developmental participation is supported by human disease and comparative mouse loss-of-function (PMIDs17675462/12097390). Purified domain self-association (PMIDs14967045/20696394) remains distinct from physiological receptor stoichiometry. Full 2022 Science structural texts could not be recovered after normal refresh/publisher attempts; their abstracts directly establish human IgM-BCR composition. Other original source-access limitations remain explicit rather than relabeled as newly read full text.
All original annotation payloads, evidence codes, supporting entities, relationship fields and flags are preserved. Review decisions judge biological claims; ordinary relationship qualifiers are not used to change their meaning. No new annotation rows were proposed. Actual Falcon and perplexity-lite attempts failed authentication/quota; manual source inspection is documented here instead of a fabricated provider report. The existing PIK3R1 provider report was reused as discovery, with primary evidence assessed separately.
The whole-receptor contribution remains ACCEPT for all three GO0004888 assertions, independent of ordinary source qualifiers. Human structure and loss/rescue support the contribution; an isolated-chain receptor or CD79A-specific BLNK scaffold is not inferred. No enables-to-contributes source defect is asserted without independent evidence of a source error. Module notes now explain the free-text contribution descriptor.