FYB1/ADAP coordinates signaling proteins, membrane recruitment and actin-associated adhesion responses. The review distinguishes its intracellular adaptor activity from direct receptor binding, the inside-out activation of integrins from ligand-initiated outside-in signaling, and natural products from the tagged fragments used in individual experiments.
PMID:10747096(https://pubmed.ncbi.nlm.nih.gov/10747096/), selected original Methods, Results and Figures 3–9, supports human FYB association with Ena/VASP and SLP-76/Nck/WASP machinery at the actin interface. It does not establish direct FYB–TCR binding. The existing signaling-receptor-binding assertion is therefore changed laterally to signaling adaptor activity, GO:0035591. The biochemical complex observation is an association result, not proof that all partners bind one another directly.
PMID:16980616(https://pubmed.ncbi.nlm.nih.gov/16980616/), selected original Methods and Results/Figures 3–7, separates plasma-membrane recruitment of Rap1 machinery from Rap1 nucleotide loading. PMID:17403904(https://pmc.ncbi.nlm.nih.gov/articles/PMC1900018/), Methods and Figures 4 and 7, distinguishes human primary T-cell/Jurkat observations from mouse experiments and SKAP-mediated linkage from direct ADAP–RIAM contact. These studies support signaling organization and recruitment, not a FYB guanine-nucleotide-exchange activity. The new GO:0033630 assertion describes positive regulation of integrin-mediated adhesion: wild-type ADAP enhances stimulated Jurkat adhesion, its SKAP-binding disruption loses this enhancement, and engineered membrane-targeted chimeras can induce adhesion without TCR stimulation. The latter constitutive effect is specific to the engineered constructs. GO:0033622 is not added as a second integrin-assembly assertion.
PMID:19996090(https://pmc.ncbi.nlm.nih.gov/articles/PMC2844019/), indexed original Methods and Results/Figures 2–3/6, provides mouse ADAP outside-in platelet evidence under shear, including direct integrin activation that fails to rescue the defect. PMID:15572693(https://pmc.ncbi.nlm.nih.gov/articles/PMC533979/), indexed Methods/Results/Figure 5, instead studies mouse Pram1. Official donor annotation connects that separate protein to the integrin-signaling IBD. TCR-driven inside-out adhesion alone is not used as evidence for the ligand-initiated GO:0007229 definition. The selected indexed original sections were actually read; failed direct PMC, bodyless XML and failed Europe PMC responses remain excluded as full-text evidence.
The actual PTHR16830 tree and alignment place human FYB1 at AN66/PTN002497673 with the exact 783-residue sequence. AN3/PTN001047914 and AN0/PTN002314453 are genuine ancestors. Mouse Pram1, mouse Fyb1 and human FYB2 donors retain their distinct identities. A single donor is not intrinsically weak evidence, and self-membership is not circularity.
Official InterPro IPR035540 maps the human C-terminal hSH3 region. Authentic original abstracts PMID:15843031(https://pubmed.ncbi.nlm.nih.gov/15843031/) and PMID:16831444(https://pubmed.ncbi.nlm.nih.gov/16831444/) support phosphatidylserine binding (GO:0001786) and phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), both verified phospholipid-binding descendants. The latter paper explicitly names PS-containing and PI(4,5)P2-containing liposomes. Full quantitative constructs and conditions were not inspected. No exclusive individual phosphoinositide preference or current product specificity is inferred, and an altered conventional SH3 recognition surface does not erase independently supported noncanonical SKAP binding.
The positive generic-binding observations without a source-established domain refinement are retained as non-core under the project curation instructions. Four contexts are refined: PMID:10409671/FYN and PMID:10570256/SLP-76 to SH2 domain binding, and the two PMID:17474147/FYN or NCK1 peptide-array contexts to SH3 domain binding. The FYB protein/peptide is the ligand for the partner domain. Each original partner and evidence context remains intact. They are not promoted to one stable all-partner complex or used as substitutes for a specific catalytic function.
PMID:17474147 uses the FYB 413–426 peptide and FYN/NCK1 domain constructs. PMID:22074159 uses a FYB 586–600 phospho-Tyr595 peptide in a peptide-protein recovery experiment. These exact ranges and target-table locators come from positive official IntAct records; the original target supplements were not directly inspected. PMID:19798671 supports tagged ADAP/SKAP1 co-purification in Jurkat cells. PMID:25814554 main Methods were read, but exact FYB 488–783 partner and kinase conditions remain source-qualified through IntAct; human proteins were tested in a yeast host.
The PMID:16461356 secondary interaction has the reverse orientation: ADAP supplies its SH3c domain and recognizes a SKAP motif. It is not mechanically relabeled as FYB binding an SH3 domain. Its described primary SKAP-SH3 contact and the separate PMID:9748251 evidence remain distinguished from the measured secondary interaction.
The actual original PMID:20534575(https://pubmed.ncbi.nlm.nih.gov/20534575/), Figure 2B and associated Results, independently verifies endogenous human ADAP–SLP-76 co-immunoprecipitation. The paper's other ZAP-70 feedback conclusions are not assigned wholesale to FYB1. The precise FYB1 comparison in PMID:27335501 remains inaccessible; the abstract's principal FYB2/ARAP target is not evidence of a wrong-gene citation. That annotation remains UNDECIDED, preserving its four separate partner groups.
PMID:15849195(https://pubmed.ncbi.nlm.nih.gov/15849195/), authentic original abstract, reports ADAP-dependent protection of SKAP55 in human Jurkat cells, reduced proteolysis after ADAP restoration, and loss of protection after disrupting the SKAP55 SH3 interaction. The new protein-stabilization assertion (GO:0050821) describes this binding-dependent protective contribution, not a protease or folding-enzyme activity. Full original Methods/figures were not read, and the quantitative result is not extended to SKAP2.
The two new process terms have no is_a/part_of ancestor–descendant redundancy with the original terms or each other. Official comparator annotation checks retain both positives and exact-term absences: noncatalytic protectors BAG3/CDC37 support the stabilization convention, while SKAP1 carries a narrower positive integrin-adhesion regulatory annotation. These comparisons inform convention; the FYB1 assertions rest on its own experiments. The complete cached GO-CAM index at the recorded current-main commit has no FYB1 hit; no claim is made about all external models.
The existing broad immune-response annotation remains non-core. Official is_a-only ancestry places TCR signaling under positive regulation of immune response, not under immune response itself. A regulatory relation is not a typed entailment that justifies TOO_GENERAL.
Human FYB membrane recruitment and cytosolic association are supported by the selected primary experiments and curated Reactome event summaries. The two Reactome events support cytosol; their full participant trees were not recovered. Auxiliary broad pathways supply metadata only and create no new process annotation.
The nuclear UniProt comment is a PROSITE-ProRule prediction. PMID:9207119 describes putative localization motifs; PMID:9671755's FYB imaging is cytoplasmic/perinuclear, whereas its separate nuclear observation concerns SKAP55. PMID:19807924's nuclear label is explicitly imported from UniProt, not a new imaging result. Both nuclear annotations remain UNDECIDED rather than being rejected from absence of evidence.
PMID:21881001(https://pmc.ncbi.nlm.nih.gov/articles/PMC3233801/), selected original Methods/Results/Figures, supports a specialized podocyte cell-contact context. Human and mouse endogenous localization, mouse kidney two-hybrid fragments and tagged MDCK assays remain separate. The broad complex row is non-core; a mouse MIST–SLAP-130–SKAP55 association abstract and independent human functional/purification evidence do not imply that every observed interactor forms one stable entity.
UniProt documents three exact sequences of 783, 829 and 839 residues. Historical short/long FYB proteins, phosphorylation-site mutants, tags and isolated domains are not automatically assigned to a current natural product. Distinct functional contributions remain unresolved.
The review YAML contains the 50 source-specific reference assessments and current annotation judgments. The evidence record preserves the complete original annotation contexts, documented product sequences, source-access boundaries and quotation locators. All 35 original contexts have explicit genuine native and TSV joins; two separately authored process additions bring the current review to 37 entries without inventing native GOA rows. The 47 normal sources comprise 25 unchanged main files and 22 newly acquired files; all three PTHR16830 family sources were reused unchanged.
The source-access record distinguishes selected original main text, indexed original sections, authentic abstracts and curated IntAct target records. Failed retrievals and bodyless XML responses are excluded from full-text claims. Survey reference identity does not imply that an FYB-specific peptide, clone or spectrum was inspected.
Nine short supporting-text associations cover the retained adaptor/recruitment excerpts and selected domain, lipid, outside-in, stabilization and regulatory-adhesion claims. Every excerpt matches the immutable normal cache; the two PMID:16980616 excerpts total 25 words, and the new adhesion excerpt is explicitly scoped to engineered membrane targeting. The PMID:10747096 excerpt retains the cache’s newline before “present”; its words are unchanged. The evidence record gives the actual byte offsets. No source cache was altered.