FYB1

Summary: The cited function is intracellular signaling-adaptor activity rather than demonstrated binding to a signaling receptor.

Reason: PMID:10747096 studies human FYB/SLAP, Ena/VASP interactions and assembly with SLP-76, Nck and WASP at the actin interface. Its selected Results and Methods support coordination of signaling proteins, not direct binding of FYB to the T-cell receptor. GO:0035591 describes a noncatalytic molecule that brings signaling components together. This is a lateral correction of the asserted molecular function, not a claim that adaptor activity is a child of receptor binding. The human short and long constructs and tested fragments are retained as historical experiment details; they do not establish identical activity of every current product.

Proposed replacements: signaling adaptor activity

Summary: Phosphorylated FYB recruits the FYN-T SH2 domain.

Reason: The original PMID:10409671 abstract explicitly states that FYN-T phosphorylation makes FYB a template for recruitment of FYN-T and SLP-76 SH2 domain binding. Thus the literal FYN partner context supports SH2 domain binding more specifically than generic protein binding. This is the direction FYB ligand to partner SH2 domain; it does not assign a kinase activity to FYB. Full construct-level Methods were not recovered, so no present-day isoform, purified affinity or stoichiometry is asserted.

Proposed replacements: SH2 domain binding

Summary: FYB phosphotyrosine sites recruit the SLP-76 SH2 domain.

Reason: The authentic PMID:10570256 abstract explicitly identifies FYB as the recruitment template for SLP-76 SH2 domains and maps the SLP-76 interaction to FYB Tyr595 and Tyr651 in Jurkat cells. This supports SH2 domain binding for the unchanged Q13094 partner. Historical residue numbers are preserved as reported; no current natural product mapping or purified binary affinity is inferred from the abstract.

Proposed replacements: SH2 domain binding

Summary: Retain the independent Jurkat SLP-76 association.

Reason: PMID:10671560 explicitly reports a functional SLAP-130–SLP-76 association in Jurkat cells in its authentic abstract. Its overexpression effects and signaling measurements remain source-specific; they do not imply a universal positive or negative effect of FYB1 on all TCR outputs. Full Methods and constructs were not recovered. The literal Q13094 partner and positive generic interaction are retained without inventing affinity, product specificity or an extra catalytic activity.

Summary: Retain the noncanonical SKAP1 interaction.

Reason: The authentic PMID:16461356 abstract reports SKAP-55 motif binding to the ADAP SH3c domain and a reduction in binding following phosphorylation of the relevant SKAP tyrosine. This is positive source-specific evidence for the Q86WV1 SKAP1 interaction. The noncanonical ligand mechanism is compatible with an hSH3 fold that does not behave as a conventional proline-rich-peptide receptor. Full construct and quantitative assay details were not inspected, and no current natural product is assigned.

Summary: The FYB 413–426 peptide binds the tested FYN SH3 domain.

Reason: PMID:17474147 uses a panel of isolated human SH3 domains in peptide-array target screening. The retained exact IntAct record EBI-1962807 identifies human FYB 413–426 as the ligand and FYN 82–143 as the domain construct, with original Table S2/data supplied by the authors as its locator. The direction supports SH3 domain binding, not an SH3 catalytic activity. The original target table was not independently read; construct-specific attribution remains to the official record, and a peptide signal does not establish full-length endogenous complex stoichiometry or a tested natural product.

Proposed replacements: SH3 domain binding

Summary: The FYB 413–426 peptide binds the tested NCK1 SH3 domains.

Reason: The PMID:17474147 SH3-domain peptide-array design and retained exact IntAct records EBI-1969425 and EBI-1966201 identify human FYB 413–426 as ligand for NCK1 constructs 2–61 and 190–252. This directional evidence supports SH3 domain binding for the unchanged P16333 partner. The target-table/construct attribution comes from official curation; the original supplementary table was not independently read. Human protein identity is distinct from the in-vitro host, and no full-length physiological stoichiometry or current natural isoform is assigned.

Proposed replacements: SH3 domain binding

Summary: Retain SKAP1 co-purification in the ADAP interaction experiment.

Reason: PMID:19798671 describes S3S-tagged ADAP purification in Jurkat cells. The authentic abstract and official IntAct entries support positive SKAP1 co-purification, with a Table 1 mass-spectrometry record and Figure 3B immunoblot record. These are association/purification observations, not a purified binary affinity assay. The tag is an experimental construct feature rather than a natural isoform. Retain Q86WV1 and the positive generic binding as non-core.

Summary: Retain endogenous human ADAP–SLP-76 association.

Reason: The actual selected full original PMID:20534575 Results and Figure 2B describe ADAP recovery in anti-SLP-76 precipitates from resting and stimulated Jurkat cells as a positive control. This directly supports the Q13094 association. The paper’s principal ZAP-70 feedback findings are not transferred wholesale to FYB1, and the unread supplementary material is not claimed as inspected. Co-immunoprecipitation does not by itself establish purified direct contact.

Summary: Retain NCK2 recovery with the phosphorylated ADAP peptide.

Reason: Official PMID:22074159 IntAct records identify O43639 NCK2 in the peptide-protein mass-spectrometry experiment using ADAP residues 586–600 with phosphorylated Tyr595. The authentic abstract and curated Table 1 locator support the positive association; the exact original table was not read. This peptide-associated recovery does not prove an isolated binary interaction or identify a current natural FYB1 product. Retain the non-core generic binding assertion.

Summary: Retain the distinct NCK1 peptide-associated recovery.

Reason: PMID:22074159 has a separate literal P16333 NCK1 context. The official curated entry derives from the same expanded peptide-protein experiment as the NCK2 and LCP2 records, using the ADAP 586–600 phospho-Tyr595 peptide. Preserve that provenance rather than treating the three expanded partners as three independently demonstrated purified binary contacts. The source-specific positive association remains non-core; full original target-table inspection was unavailable.

Summary: Retain LCP2 recovery in the ADAP phosphopeptide experiment.

Reason: The exact Q13094 context in PMID:22074159 is supported by the official curated peptide-protein mass-spectrometry record for the ADAP 586–600 phospho-Tyr595 peptide. The source locator is Table 1, not an independently inspected purified binary assay. This is consistent with other SLP-76 evidence but remains a separate original annotation with its own experiment and partner. Retain it as non-core generic binding.

Summary: Retain kinase-dependent NCK2 binding in the human-protein yeast assay.

Reason: The actual PMID:25814554 main Methods explain the phosphotyrosine-dependent yeast two-hybrid design. Exact official IntAct entries join human FYB residues 488–783 with O43639 NCK2 under kinase conditions including FYN or YES1. Human protein identity does not make the yeast host a human-cell assay, and study-wide full-length descriptions do not override this fragment-specific record. The supplementary target rows were not directly inspected. Retain the positive generic association as non-core.

Summary: Retain the source-specific FYN interaction from the phosphotyrosine-dependent screen.

Reason: PMID:25814554 official records identify FYB 488–783 and a FYN construct including residues 115–537, with a human-protein yeast two-hybrid readout. The selected original Methods were read, while the exact original supplementary row remains source-qualified through IntAct. Preserve P06241 and the kinase-dependent experimental context without claiming that all products bind constitutively or that this screen establishes an endogenous stoichiometric complex.

Summary: Retain LCP2 association with the tested FYB fragment.

Reason: The exact PMID:25814554 IntAct entries support Q13094 LCP2 association with human FYB 488–783 in the phosphotyrosine-dependent yeast system, with the recorded kinase conditions preserved. Main original Methods were inspected, not the source’s complete target supplement. The fragment and yeast host are explicit assay limits; this remains a positive non-core interaction rather than evidence for a unique present-day isoform or direct physiological catalytic function.

Summary: The exact FYB1 comparison and four-partner assertion remain unverified in the ARAP original.

Reason: PMID:27335501 foregrounds ARAP, now FYB2, in the authentic abstract. That does not establish a wrong-gene citation: a full comparison could include FYB1/ADAP. The relevant original Methods/Results and exact FYB1 target records were not recovered, and the bounded official IntAct capture did not supply a matching source record. Preserve all four literal WITH/FROM groups for P06239, P06241, Q13094 and Q86WV1 without inventing an all-at-once complex or substituting FYB2 results. Use UNDECIDED pending the exact comparison experiment.

Summary: Nuclear localization remains a prediction without a verified FYB1 localization experiment.

Reason: The literal UniProt subcellular-location mapping is retained. The current nuclear comment is supported by a PROSITE-ProRule prediction, and PMID:9207119 discusses putative nuclear-localization sequences. The inspected PMID:9671755 imaging reports FYB mainly in the cytoplasm; its separate nuclear paragraph concerns SKAP55, not FYB. These observations do not establish absence of a context-dependent FYB1 nuclear pool, but they do not verify the nuclear assertion. Keep the annotation UNDECIDED rather than treating a predicted motif as an assay or making a confident misattribution claim.

Summary: The original TAS source supplies a putative targeting motif rather than a verified nuclear location.

Reason: The actual selected PMID:9207119 original identifies putative nuclear-localization sequences in FYB; a direct FYB nuclear-localization experiment was not found in the inspected sections. The later source’s SKAP55 nuclear result must not be assigned to FYB. This is an unresolved evidence boundary, not proof that FYB1 can never enter nuclei. Preserve the original TAS/PMID context and defer a definitive disposition pending a target-specific localization assay.

Summary: Preserve the positive cytoplasmic experiment while using retained cytosol coverage for specificity.

Reason: PMID:9671755 Figure 5 and selected Results describe tagged FYB as mainly cytoplasmic/perinuclear with occasional membrane signal in the stated expression systems; human protein identity is distinguished from the host. The annotation is not rejected. At the gene level, the independently supported cytosol location is a verified part_of refinement of cytoplasm and is retained in other existing rows. No claim is made that this historical image alone excludes all organellar association.

Summary: Cytosol provides more informative coverage of the intracellular adaptor pool.

Reason: The broad cytoplasmic location is biologically consistent with FYB1. The retained cytosol annotations, human fractionation/association work and cytoplasmic imaging support a more informative gene-level location. The official ontology explicitly places cytosol part_of cytoplasm. This granularity decision does not deny the original UniProt mapping or require that every historical assay resolve organelles. Plasma-membrane recruitment and actin-associated pools remain separately represented.

Summary: Reactome models recruitment of cytosolic FYB1 into a SIRPA-associated adaptor complex.

Reason: The retained curated event R-HSA-391151 recruits FYB through SKAP2 to the phosphorylated SIRPA complex and includes cytosol as a compartment. This supports the incoming cytosolic localization of the adaptor. The event does not establish an isolated direct FYB1–SIRPA receptor-binding activity, a current isoform-specific mechanism, or the cellular location of every component.

Summary: Reactome places the association of phosphorylated SLP-76 with ADAP/FYB1 in the cytosol.

Reason: The retained curated R-HSA-430135 event and official compartment metadata support cytosolic FYB1 association with SLP-76. The summary separately discusses platelet association and knockout-mouse phenotypes; those are not relabeled as direct human experiments or assigned to individual natural products. Cytosolic localization is appropriate for this intracellular adaptor.

Summary: Retain the conserved plasma-membrane-associated location.

Reason: The AN0/PTN002314453 placement and human descent are verified, with the literal mouse Fyb1 and human FYB2 donor set preserved. Independent human Jurkat fractionation in PMID:17403904 Figure 7B shows ADAP recruitment to the plasma membrane; primary-cell association and earlier cortical/adhesion imaging are consistent with this context. This is peripheral recruitment of an intracellular adaptor, not a transmembrane topology claim or a claim of constant residence in every cell. The original qualifier is preserved without creating a separate action hierarchy.

Summary: The transferred plasma-membrane location agrees with independent human FYB1 recruitment.

Reason: Retain the literal O35601/Ensembl/InterPro provenance. O35601 is verified mouse Fyb1, and its current plasma-membrane experiment points to PMID:17403904. That selected original also contains an independent human Jurkat ADAP fractionation result in Figure 7B. The membrane-associated adaptor pool is therefore consistent with human evidence as well as orthology. The mouse and human experiments are not collapsed, and the row remains an electronic inference rather than being relabeled as an assay.

Summary: Broad immune-response context is retained separately from the defined TCR signaling function.

Reason: Selected PMID:9207119 original human association and separately identified mouse cytokine experiments, together with later human T-cell evidence, support immune-response context. This broad physiological context remains non-core, while signaling adaptor activity and TCR signaling define the mechanism. The official is_a-only ancestry of GO:0050852 reaches positive regulation of immune response (GO:0050778), not immune response (GO:0006955); a regulatory relation does not establish the direct typed entailment needed for TOO_GENERAL. No murine cytokine assay is relabeled as human.

Summary: Retain the actual ancestral integrin-signaling assertion and its distinct PRAM1 donor evidence.

Reason: The literal IBD maps to AN3/PTN001047914 on the verified human FYB1 lineage. Its MGI:3576625 donor is mouse Pram1/Q6BCL1, not mouse FYB1; official donor GOA links the term to PMID:15572693. That original’s selected Methods/Results show integrin-dependent outside-in defects in Pram1-null neutrophils, distinct from cytokine-induced inside-out activation. Separately, PMID:19996090 establishes a matching outside-in role for mouse ADAP. These observations support the inherited adaptor function; the valid node is not challenged for having a single donor. Human FYB1, mouse ADAP and mouse Pram1 experiments remain separate.

Summary: The integrin-signaling inference is consistent with independently established outside-in adaptor function.

Reason: Retain the literal InterPro IPR043443 assertion. GO:0007229 is ligand-initiated integrin signaling, so TCR-driven inside-out integrin activation alone was not used to justify it. Selected original PMID:19996090 Methods and Results show impaired outside-in signaling in mouse ADAP-null platelets under shear even when manganese directly activates integrin. This ortholog experiment supports the conserved FYB1 adaptor role, with human membrane/actin organization established independently. It is not a direct human platelet knockout assay or a new process assertion.

Summary: The mapped hSH3 region supports phosphatidylinositol-4,5-bisphosphate and phosphatidylserine binding.

Reason: Official InterPro IPR035540 maps to human FYB1. Original PMID:15843031 reports hSH3 binding to acidic lipids, including PS and polyvalent phosphoinositides; PMID:16831444 explicitly reports interaction with PS-containing liposomes and a single-site, non-cooperative interaction with PI(4,5)P2-containing liposomes. These support the two named phospholipid-binding descendants without requiring exclusive lipid preference. Both descend from phospholipid binding by official is_a ancestry. The authentic abstracts were read, not full quantitative Methods; no equivalent affinity, uniform behavior of all SH3 domains or current product specificity is claimed.

Proposed replacements: phosphatidylinositol-4,5-bisphosphate binding phosphatidylserine binding

Summary: Association with the actin cytoskeleton is part of FYB1’s signaling organization.

Reason: The selected actual PMID:10747096 original connects human FYB with Ena/VASP and actin-regulatory signaling complexes and localizes FYB at adhesion/lamellipodial structures. This supports the actin-cytoskeleton-associated adaptor pool. The evidence does not make FYB an actin polymerase, imply direct catalysis of nucleation, or erase the distinction between peptide competition and a FYB knockout. Historical short/long constructs and fragments are not assumed to test all current products.

Summary: Retain broad complex association without treating every co-precipitated partner as one stable assembly.

Reason: The original O35601/Ensembl transfer remains intact. The mouse donor’s source PMID:12681493 authentic abstract describes an associated MIST–SLAP-130–SKAP55 signaling complex, but its full purification and construct details were not inspected. Independent human ADAP/SKAP work includes tandem-affinity purification and functional organization of a defined signaling module. These together support broad complex-associated context, retained as non-core. They do not establish that all fifteen interaction annotations form a single stable complex, and no specific in_complex term is added from a bare co-immunoprecipitation alone.

Summary: Retain inherited participation in T-cell receptor signaling.

Reason: The actual AN3/PTN001047914 IBD lies on the human FYB1 lineage, and its literal Q5VWT5 donor is human FYB2/ARAP. The phylogenetic assertion is supported independently for FYB1 by human T-cell FYN–FYB–SLP-76 cooperation and ADAP/SKAP-dependent signaling organization. A different paralog among the descendant evidences is not a transfer error when the curator’s ancestral placement and target descent are verified. No FYB2-specific construct is relabeled as FYB1.

Summary: T-cell receptor signaling is a central FYB1 adaptor process.

Reason: The selected full PMID:9207119 original establishes FYB association with FYN and SLP-76 and a TCR-linked signaling role, with human and mouse systems explicitly distinguished. Later human Jurkat experiments provide direct functional evidence that FYB interaction modules coordinate TCR responses. Preserve the TAS provenance and avoid converting the reported murine IL-2 assay into a human experiment. The gene product performs signaling organization itself rather than merely being a required substrate.

Summary: Retain the electronic junctional context with its specialized cell-type scope.

Reason: The literal UniProt anchoring-junction mapping is consistent with the independently inspected PMID:21881001 podocyte study and its mouse-donor chain. The source includes human/mouse endogenous localization and separate tagged MDCK assays; these are not interchangeable with a direct assay of every human product. Retain the positive specialized location as non-core, without promoting FYB1 to a structural junction protein in all tissues or claiming a new junction-assembly process.

Summary: Retain the context-specific anchoring-junction association.

Reason: The exact donor O35601 is mouse Fyb1, whose current anchoring-junction source is PMID:21881001. The selected original studies endogenous ADAP in cultured human and mouse podocytes and cell-contact localization, alongside tagged interaction experiments in MDCK cells. Preserve those organism and host boundaries. This specialized junctional context is compatible with FYB1 biology but is not the central hematopoietic signaling location synthesized as core. The transferred ISS assertion is retained without inventing an exact natural isoform.

Summary: FYB1 organizes recruitment of signaling proteins to the plasma membrane.

Reason: The exact AN0/PTN002314453 IBD is an ancestor of the human FYB1 sequence and retains its mouse Fyb1 donor. Selected original PMID:16980616 reports ADAP/SKAP-dependent plasma-membrane localization of Rap1 in human Jurkat cells and complementary mouse knockout experiments. PMID:17403904 separates the ADAP/SKAP/RIAM assembly from direct ADAP–Rap1 contact and shows relocation of the signaling module. This supports localization machinery as FYB1’s own adaptor contribution, without assigning Rap1 nucleotide-exchange activity to FYB1.

Summary: FYB1 protects its associated SKAP1 partner from degradation in human T cells.

Reason: The authentic PMID:15849195 abstract reports that restoring ADAP to an ADAP-deficient human Jurkat line slows SKAP55 proteolysis fivefold; disruption of the SKAP55 SH3 interaction blocks protection. FYB1 therefore contributes the binding-dependent protective function rather than serving as the protein being stabilized. The measured partner is SKAP1/SKAP55; the quantitative result is not extended to SKAP2, and no protease or folding-enzyme activity is inferred. This narrow perturbation-supported process is distinct from the existing signaling and localization terms. The complete authentic abstract was read, not the original full Methods or figures.

Summary: FYB1 organizes an ADAP/SKAP55 module that promotes integrin-mediated T-cell adhesion.

Reason: Selected original PMID:16980616 Methods and Results/Figures 3–7 show that tagged human ADAP enhances stimulated Jurkat adhesion to ICAM-1 and fibronectin, whereas disruption of its SKAP-binding region fails to support that enhancement; competing interaction fragments inhibit the response. Engineered LAT-mediated membrane targeting of the ADAP/SKAP55 module can induce adhesion without TCR stimulation. That constitutive result belongs to the engineered chimera, not unqualified wild-type FYB1 or a current natural product. FYB1 supplies a scaffold/recruitment contribution upstream of the measured adhesion endpoint, not integrin catalysis or Rap1 nucleotide exchange. PMID:17403904 corroborates module assembly and recruitment with human and mouse experiments kept distinct and SKAP-mediated linkage distinguished from direct ADAP–RIAM binding. The regulatory adhesion term is preferred to a separate integrin-assembly assertion and is distinct from the existing ligand-initiated outside-in signaling term.