BLNK (SLP-65/BASH) is a noncatalytic adaptor that organizes signaling downstream of the B-cell antigen receptor. Its phosphorylated tyrosines and proline-rich motifs recruit effectors including phospholipase Cgamma, VAV, GRB2 and NCK, coupling SYK-dependent receptor-proximal events to calcium mobilization and downstream signaling. Constitutive association with CIN85 and binding to lipid vesicles help assemble cytoplasmic signaling granules that can be recruited to activated receptor sites at the plasma membrane. BLNK supplies docking and spatial organization, while associated kinases and phospholipases perform the enzymatic reactions. Disruption of human BLNK can arrest the transition from pro-B to pre-B cells and cause antibody deficiency.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005068 transmembrane receptor protein tyrosine kinase adaptor activity | TAS PMID:9697839 BLNK: a central linker protein in B cell activation. | MODIFY | Summary: Generalize the receptor-tyrosine-kinase-specific adaptor term to signaling adaptor activity. Reason: The original paper identifies BLNK as the linker between BCR-associated SYK and downstream effectors. GO:0005068 requires a transmembrane receptor that is itself a protein tyrosine kinase; BCR-associated cytosolic SYK is not such a receptor. The demonstrated noncatalytic assembly function is accurately captured by GO:0035591. This corrects the receptor-class restriction of this TAS assertion without asserting that BLNK can never interact with an RTK in another context. Proposed replacements: signaling adaptor activity Supporting Evidence: PMID:9697839 provides docking sites |
| GO:0005515 protein binding | IPI PMID:16912232 Human SLP-65 isoforms contribute differently to activation a... | MODIFY | Summary: Specify the experimentally described GRB2 SH3-domain interaction. Reason: The complete abstract explicitly assigns association with GRB2 to an atypical SH3-domain-binding motif in the long human SLP-65 form. SH3 domain binding is therefore more informative than generic protein binding. This historical long-versus-short comparison is not automatically mapped onto all three current UniProt alternative products; the original unspecific source object is preserved. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:16912232 an atypical SH3 domain-binding motif |
| GO:0005515 protein binding | IPI PMID:16969585 Solution structure and phosphopeptide binding of the SH2 dom... | UNDECIDED | Summary: The source-specific BLNK–BTK interaction requires accessible primary assay details. Reason: The normal cache contains the citation but no abstract or full text, and the publisher access attempt did not recover the article. Its title concerns the human BTK SH2 domain; that does not establish or refute which BLNK peptide was tested. BTK recruitment is compatible with the independently documented BLNK signalosome, but the exact interaction in this NMR citation is not independently adjudicated. Preserve the IPI assertion and partner Q06187 pending the original binding experiment. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21822214 The B-cell antigen receptor signals through a preformed tran... | MODIFY | Summary: Refine the GRB2 interaction to SH3 domain binding. Reason: Selected Results identify GRB2 among SLP65 partners and show that the proline/arginine docking peptide enriches GRB2, at a weaker score than CIN85 and CD2AP. The human long-form study independently establishes the GRB2 SH3 interaction. The refinement describes this binding interface, not equal functional contributions of these three partners. Proposed replacements: SH3 domain binding |
| GO:0005515 protein binding | IPI PMID:21822214 The B-cell antigen receptor signals through a preformed tran... | MODIFY | Summary: Specify binding to the SH3 domains of CIN85. Reason: The source partner Q5ZMQ7 is a chicken SH3KBP1/CIN85 accession, verified through the NCBI chicken SH3KBP1 record; it is not relabeled as a human partner. Selected Results map SLP65 proline/arginine motifs to CIN85 SH3 domains using mutations, GST-domain pulldowns and recombinant binding. The paper combines avian interactomics with human and murine corroboration. This warrants SH3 domain binding while preserving the xenolog source partner. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:21822214 the interaction is direct |
| GO:0005515 protein binding | IPI PMID:21822214 The B-cell antigen receptor signals through a preformed tran... | MODIFY | Summary: Specify the CD2AP SH3-domain binding interface. Reason: Selected Results show loss of CD2AP association after mutation of the three SLP65 proline/arginine motifs and binding to a GST fusion containing CD2AP SH3 domains. The human CD2AP constructs are specified in Methods. CD2AP can partly substitute for CIN85 in the tested system, but is not asserted to be an equally essential signalosome component. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:21822214 three SH3 domains of CD2AP |
| GO:0005515 protein binding | IPI PMID:21930792 SCIMP, a transmembrane adaptor protein involved in major his... | MODIFY | Summary: Refine the SCIMP interaction to recognition of phosphorylated tyrosine by BLNK. Reason: BLNK's own SH2 domain recognizes SCIMP phosphorylated at Tyr131, as recorded in the normal UniProt entry citing this paper. The primary Ramos-cell mutagenesis identifies SCIMP Y131 as the SLP65 recruitment site; cooperative GRB2 binding remains explicit. These data support phosphotyrosine residue binding without requiring a purified isolated pair. MHC-II signaling remains a contextual role. GO:0042169 describes binding to another protein's SH2 domain, the reciprocal direction, so it does not capture this activity. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:21930792 When phosphorylated, SCIMP binds to the SLP65 adaptor protein |
| GO:0005515 protein binding | IPI PMID:24728074 Enhanced prediction of Src homology 2 (SH2) domain binding p... | UNDECIDED | Summary: The exact BLNK–androgen receptor domain/peptide measurement remains unadjudicated. Reason: The source reports a large fluorescence-polarization survey of purified SH2 domains against synthetic phosphotyrosine peptides, including androgen receptor. The selected Methods, receptor-specific Results and Discussion were read, but the cached body does not identify BLNK by name and the pair-level supplementary table was not recovered. This does not contradict the curated IPI partner P10275. Retain the source assertion as unresolved rather than infer a physiological full-length interaction, remove it from abstract emphasis, or propose a more specific partner-class term without the exact measurement. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24728074 Enhanced prediction of Src homology 2 (SH2) domain binding p... | UNDECIDED | Summary: The exact BLNK–KIT domain/peptide measurement remains unadjudicated. Reason: The source reports a large fluorescence-polarization survey of purified SH2 domains against synthetic phosphotyrosine peptides, including KIT. The selected Methods, receptor-specific Results and Discussion were read, but the cached body does not identify BLNK by name and the pair-level supplementary table was not recovered. This does not contradict the curated IPI partner P10721. Retain the source assertion as unresolved rather than infer a physiological full-length interaction, remove it from abstract emphasis, or propose a more specific partner-class term without the exact measurement. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:9697839 BLNK: a central linker protein in B cell activation. | MODIFY | Summary: Specify binding to the VAV SH2 domain. Reason: The original BLNK paper identifies VAV among SH2-containing effectors recruited to phosphorylated BLNK. The earlier biochemical abstract explicitly locates the pp70/pp68–VAV interaction in the VAV SH2 domain. Together these support the interface-level refinement of the preserved VAV1 partner P15498. BLNK supplies docking sites; VAV supplies guanine-nucleotide exchange activity. Proposed replacements: SH2 domain binding |
| GO:0005515 protein binding | IPI PMID:9697839 BLNK: a central linker protein in B cell activation. | MODIFY | Summary: Specify the SH2-mediated NCK interaction. Reason: The original source describes NCK among the SH2-containing effectors recruited to docking sites created by SYK phosphorylation of BLNK. SH2 domain binding describes the binding function more precisely than generic protein binding. No kinase or exchange-factor chemistry is attributed to either adaptor. Proposed replacements: SH2 domain binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:9697839 BLNK: a central linker protein in B cell activation. | MODIFY | Summary: Specify the SH2-dependent component of GRB2 recruitment. Reason: The original source places GRB2 among SH2-containing effectors binding phosphorylated BLNK. The earlier biochemical abstract reports cooperative SH2 and SH3 requirements for GRB2 association with the B-cell pp70/pp68 proteins. SH2 domain binding captures the phosphotyrosine-dependent interface here; the separately reviewed long-form GRB2 interaction captures SH3 binding. The historical molecular-weight species are not assigned to current alternative-product identifiers. Proposed replacements: SH2 domain binding |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasmic activity is consistent with the inherited adaptor function. Reason: The local PTHR14098 PAINT record places cytoplasm at ancestral node PTN001019935 with experimental descendants from this adaptor family, including BLNK. The target appearing among descendants is valid experimental grounding, not circularity. Cytosolic pools, vesicle-associated granules and stimulus-dependent membrane recruitment independently agree with the broad cytoplasmic location. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Retain the broad cytoplasmic localization inference. Reason: This combined electronic annotation records mouse orthology and UniProt subcellular-location evidence. Independent localization and reconstitution studies show cytoplasmic BLNK before recruitment to activated receptor sites. The term is broad but compatible with both soluble and granule-associated pools; it does not imply exclusive cytosolic solubility. |
| GO:0005829 cytosol | IDA PMID:9697839 BLNK: a central linker protein in B cell activation. | ACCEPT | Summary: BLNK has a cytosolic signaling pool. Reason: The source IDA localization is consistent with the UniProt record and subsequent microscopy showing redistribution from the cytosol to the plasma membrane upon BCR stimulation. Cytosolic localization is compatible with protein assemblies and vesicle-associated pools; it is not an assertion that every BLNK molecule is freely soluble. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-983703 | ACCEPT | Summary: The Reactome reaction explicitly starts with a cytosolic BLNK complex. Reason: The cached reaction describes a stable BLNK–GRB2–SOS1–CIN85 complex in the cytosol that is recruited to the plasma membrane before SYK-dependent phosphorylation. This directly supports the compartment annotation. BLNK is the adaptor/substrate in this step; SYK performs phosphorylation. Supporting Evidence: Reactome:R-HSA-983703 forms a stable complex with GRB2, SOS1, and CIN85 in the cytosol |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: Retain the plasma-membrane localization assertion. Reason: The source is curation of immunofluorescence data. Its individual image was not reread, but independent BLNK studies corroborate stimulus-dependent recruitment to BCR-containing plasma-membrane sites. The protein is a peripheral cytoplasmic adaptor, not an integral membrane receptor; the broad location term does not assert transmembrane topology. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Retain the mapped plasma-membrane location. Reason: The UniProt subcellular-location mapping is consistent with activation-dependent membrane recruitment of BLNK complexes. This describes association at the cytoplasmic membrane surface rather than a transmembrane domain. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-1112666 | ACCEPT | Summary: The plasma-membrane BLNK signalosome supports this component annotation. Reason: The Reactome event places BLNK in the membrane-associated signaling assembly supporting PLCgamma-mediated PIP2 hydrolysis. The compartment agrees with the other BLNK recruitment reaction and primary localization evidence. The hydrolytic chemistry belongs to PLCgamma; the reaction title does not assign phospholipase activity to BLNK. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9606151 | ACCEPT | Summary: Reactome explicitly places phosphorylated BLNK at the plasma membrane. Reason: The cached event states that phosphorylated BLNK at the plasma membrane recruits BTK, PLCgamma, VAV, GRB2 and NCK. This is direct pathway-context support for the location and scaffold role, without claiming that all complex partners catalyze the same reaction. Supporting Evidence: Reactome:R-HSA-9606151 Phosphorylated BLNK (also called BASH or SLP-65) at the plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9691421 | ACCEPT | Summary: Retain the compartment while distinguishing the inhibitor target. Reason: The cited event concerns inhibitor binding to BTK and its summary does not itself discuss BLNK. The source location assertion is nevertheless concordant with independently established plasma-membrane BLNK signalosomes in the adjacent recruitment event and localization experiments. It is not used as evidence that BLNK binds these drugs or has BTK kinase activity. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-983703 | ACCEPT | Summary: BLNK is recruited to the membrane before SYK phosphorylation. Reason: The cached Reactome reaction explicitly describes cytosolic BLNK complex recruitment to the plasma membrane, followed by phosphorylation by SYK. Some detailed recruitment interactions are inferred from mouse and chicken experiments as the source states; the human compartment annotation remains consistent with the broader experimental record. Supporting Evidence: Reactome:R-HSA-983703 |
| GO:0006954 inflammatory response | TAS PMID:9697839 BLNK: a central linker protein in B cell activation. | UNDECIDED | Summary: The broad inflammatory-response assignment is not resolved by the accessible source. Reason: The complete cached abstract of the original BLNK paper establishes B-cell receptor signal integration, but does not describe a separate inflammatory-response experiment or mechanism. The full source was not available in the normal cache. This is insufficient to remove the TAS annotation, yet does not justify confidently treating this broad process as the defining function. Preserve it as unresolved pending its original contextual support. Supporting Evidence: |
| GO:0006959 humoral immune response | TAS PMID:9697839 BLNK: a central linker protein in B cell activation. | KEEP AS NON CORE | Summary: Retain humoral immunity as a broader biological consequence. Reason: BLNK organizes B-cell receptor signaling, and human BLNK deficiency arrests B-cell development. These observations are consistent with a role in humoral immunity. The broad organism-level process is retained separately from the defining molecular adaptor and signalosome-assembly functions; it is not a catalytic activity. |
| GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway | IBA GO_REF:0000033 | UNDECIDED | Summary: The RTK-specific ancestral process inference needs a targeted phylogenetic/evidence check. Reason: The actual PTHR14098 PAINT row places GO:0007169 at PTN001019935 and lists mouse Clnk (MGI:1351468) as an experimental descendant. One descendant can validly seed an IBD; this is not a donor-count objection. Current GO defines a receptor that itself has tyrosine kinase activity, whereas the well-established BLNK mechanism uses a BCR coupled to non-receptor SYK. The KIT phosphopeptide screen does not alone establish a BLNK RTK signaling process. No target-specific loss or erroneous node placement has been established, and the full ancestral experimental chain was not adjudicated. Leave the IBA unresolved rather than assert over-propagation or remove it. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN001019935 · PTN001019935 UNRESOLVED The local PTHR14098 export records a non-negated IBD for GO:0007169 at this node, dated 2017-02-28. No erroneous placement or BLNK-specific functional loss is established by this review. MGI:MGI:1351468 · Clnk UNRESOLVED Official MGI identity checked; the local PAINT record lists this experimental descendant. Its complete underlying RTK experimental chain was not adjudicated. The single-descendant count is not evidence of a propagation defect. |
| GO:0008289 lipid binding | IDA PMID:32051419 Tripartite phase separation of two signal effectors with ves... | ACCEPT | Summary: BLNK directly associates with lipid vesicles. Reason: Selected Results describe recombinant SLP65 liposome flotation and a preference for small, highly curved vesicles; both neutral DOPC/DOPE and mixed lipid compositions support the vesicle-dependent assembly. This directly supports lipid binding. It does not establish selective recognition of one lipid headgroup, so a narrower lipid species is not proposed. Supporting Evidence: PMID:32051419 striking binding preference of SLP65 for SUVs |
| GO:0008289 lipid binding | IMP PMID:25140054 Macromolecular assembly of the adaptor SLP-65 at intracellul... | ACCEPT | Summary: The amino-terminal vesicle-binding module is functionally important. Reason: The complete abstract reports that the approximately 50-residue amino-terminal module anchors SLP65 to vesicles and becomes structured on noncharged membrane lipids. Its required association with resting-cell vesicular compartments supports the lipid-binding IMP assertion, corroborated by the later direct liposome assay. No phosphoinositide specificity is inferred. |
| GO:0010628 positive regulation of gene expression | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain downstream positive regulation of gene expression. Reason: The source is an Ensembl Compara orthology transfer from mouse Blnk. Independent human isoform experiments report AP1- and NF-kappaB-dependent transcription downstream of BLNK signaling. This is a plausible downstream outcome, not direct DNA binding or transcription-factor activity of BLNK, and is kept outside the molecular core. Full PMID:22949502 independently resolves the mouse donor context as inducible BLNK signaling upstream of LAPTM5 expression; the fusion experiment is not a human direct transcription assay. |
| GO:0016020 membrane | IDA PMID:9697839 BLNK: a central linker protein in B cell activation. | ACCEPT | Summary: Membrane association is supported across more than one membrane context. Reason: The broad source IDA location agrees with activation-dependent plasma-membrane recruitment and later evidence of association with intracellular lipid vesicles. Retaining the broad term avoids making membrane association exclusively plasma-membrane-specific; the more precise plasma-membrane annotations remain separately represented. |
| GO:0019899 enzyme binding | IPI PMID:9697839 BLNK: a central linker protein in B cell activation. | MODIFY | Summary: Specify binding to phospholipase Cgamma1. Reason: The source partner P19174 is PLCG1, and the original abstract explicitly identifies PLCgamma among effectors recruited by phosphorylated BLNK. Phospholipase binding is more informative than the enzyme-binding parent. BLNK provides docking support and does not hydrolyze phospholipid itself. Proposed replacements: phospholipase binding Supporting Evidence: |
| GO:0019901 protein kinase binding | IPI PMID:11606584 Tyrosine residues in phospholipase Cgamma 2 essential for th... | MODIFY | Summary: Specify binding to the non-receptor tyrosine kinase SYK. Reason: The original partner P43405 is SYK. The abstract describes purified SYK phosphorylation of BLNK in complex-assembly experiments, consistent with the curated IPI interaction. Protein tyrosine kinase binding is the appropriate more specific kinase class. This is not receptor tyrosine kinase binding, nor catalytic kinase activity by BLNK. Proposed replacements: protein tyrosine kinase binding Supporting Evidence: |
| GO:0030183 B cell differentiation | NAS PMID:10583958 An essential role for BLNK in human B cell development. | KEEP AS NON CORE | Summary: Retain the essential developmental consequence of BLNK signaling. Reason: The complete human case abstract reports a homozygous BLNK splice defect with preserved pro-B cells but absent pre-B and mature B cells. This supports the curated B-cell differentiation process as a biological outcome of BLNK signal integration. It is retained as developmental context rather than expanded into additional NEW processes from necessity alone. Supporting Evidence: PMID:10583958 no pre-B cells or mature B cells |
| GO:0035556 intracellular signal transduction | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the ancestral intracellular signal-transduction function. Reason: The actual PAINT row places this process at PTN001019935 with Clnk and BLNK experimental descendants. BLNK directly performs the scaffold work of intracellular BCR signal transmission. The broad ancestral process is sound; a target among the IBD descendants is legitimate, not circular. The more specific BCR process is separately supported. |
| GO:0035556 intracellular signal transduction | IDA PMID:11606584 Tyrosine residues in phospholipase Cgamma 2 essential for th... | ACCEPT | Summary: Purified-protein assembly supports BLNK participation in signal transmission. Reason: Although the paper focuses on PLCgamma2, its complete abstract explicitly assays SYK-dependent BLNK phosphorylation and complex assembly. Phosphorylated BLNK supplies PLCgamma2 docking sites and thus does work in the signaling process. BTK and SYK supply the distinct kinase reactions; the source is not dismissed because its title foregrounds another protein. Supporting Evidence: |
| GO:0035556 intracellular signal transduction | IDA PMID:9341187 Identification of two tyrosine phosphoproteins, pp70 and pp6... | ACCEPT | Summary: The original phosphoprotein complexes support intracellular B-cell signaling. Reason: The complete abstract reports BCR-dependent pp70/pp68 interactions with PLCgamma, GRB2 and VAV through specific SH2/SH3 interfaces, and distinguishes them from SLP76. The curated BLNK assignment is consistent with the subsequent identification paper. Historical pp70/pp68 labels are not retrospectively assigned to all current BLNK alternative products. |
| GO:0035591 signaling adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the phylogenetically supported signaling adaptor activity. Reason: The actual PTHR14098 PAINT export records GO:0035591 at PTN001019940 with human BLNK as an experimental descendant. The source on the target is valid grounding for the ancestral inference. The noncatalytic docking mechanism is directly supported by the BLNK papers. |
| GO:0035591 signaling adaptor activity | IDA PMID:11606584 Tyrosine residues in phospholipase Cgamma 2 essential for th... | ACCEPT | Summary: BLNK supplies the scaffold in the purified assembly system. Reason: The source describes purified-protein complex formation in which SYK phosphorylation of BLNK creates PLCgamma2 binding sites. That is a signaling-adaptor function of BLNK, distinct from the SYK and BTK catalytic steps and PLCgamma2 phospholipase chemistry. Supporting Evidence: PMID:11606584 providing binding sites for PLCgamma2 |
| GO:0035591 signaling adaptor activity | IDA PMID:9697839 BLNK: a central linker protein in B cell activation. | ACCEPT | Summary: Signaling adaptor activity is the central BLNK molecular function. Reason: The original source identifies BLNK as the noncatalytic linker joining BCR-associated SYK with PLCgamma, VAV, GRB2 and NCK. Its phosphorylation generates interaction sites that coordinate downstream signaling; this directly matches the GO adaptor definition. Supporting Evidence: |
| GO:0042169 SH2 domain binding | IDA PMID:9697839 BLNK: a central linker protein in B cell activation. | ACCEPT | Summary: Phosphorylated BLNK binds SH2-containing effectors. Reason: The original paper explicitly states that SYK phosphorylation of BLNK creates docking sites for SH2-containing effectors. This is binding to partner SH2 domains, not an inference made solely from BLNK possessing its own SH2 domain. Supporting Evidence: PMID:9697839 these SH2-containing effector molecules |
| GO:0043274 phospholipase binding | IPI PMID:11606584 Tyrosine residues in phospholipase Cgamma 2 essential for th... | ACCEPT | Summary: Retain the specific PLCgamma2 binding function. Reason: The abstract directly describes purified complex-assembly experiments and PLCgamma2 docking on phosphorylated BLNK. The partner P16885 is PLCG2. This establishes phospholipase binding without transferring the enzymatic phospholipid-hydrolysis activity to BLNK. Supporting Evidence: |
| GO:0050853 B cell receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the BLNK-clade BCR signaling inference. Reason: The actual PAINT row places the BCR signaling process at PTN001019940 with human BLNK experimental grounding. BLNK physically organizes the receptor-proximal effector machinery, which is participation in signal transmission rather than merely being necessary as a passive substrate. Its phosphorylation state regulates this scaffold work. |
| GO:0050853 B cell receptor signaling pathway | IDA PMID:9697839 BLNK: a central linker protein in B cell activation. | ACCEPT | Summary: BLNK directly organizes BCR signal transmission. Reason: The original identification paper links BCR-associated SYK to several downstream effectors through BLNK docking sites. BLNK is an active structural participant in the signaling step; being phosphorylated by SYK does not exhaust its role or reduce it to a passive substrate. Supporting Evidence: |
| GO:0050853 B cell receptor signaling pathway | IMP PMID:11606584 Tyrosine residues in phospholipase Cgamma 2 essential for th... | ACCEPT | Summary: The source supports BLNK-mediated assembly in the BCR pathway. Reason: The accessible source combines human PLCgamma2 reconstitution in deficient chicken DT40 cells with purified biochemical assembly. It explicitly identifies phosphorylated BLNK as the docking scaffold in that pathway. Preserve the curator-assigned IMP evidence; this review does not pretend that every assay was conducted in primary human B cells. Supporting Evidence: |
| GO:0140693 molecular condensate scaffold activity | IMP PMID:32051419 Tripartite phase separation of two signal effectors with ves... | ACCEPT | Summary: BLNK supplies a demonstrated multivalent condensate scaffold. Reason: Selected Results and Methods show phase separation of recombinant human SLP65 fragments with CIN85 and lipid vesicles, and mutation-dependent granule formation and calcium responses for human SLP65 expressed in deficient chicken DT40 cells. The multivalent protein and lipid interactions supply scaffold work, supporting the existing IMP term. Purified CIN85 includes a defined deletion construct. Human B-cell concentration measurements are distinct from the DT40 functional rescue; the authors leave in-situ vesicle organization within cellular granules as a future test. Supporting Evidence: |
| GO:1990782 protein tyrosine kinase binding | IPI PMID:9697839 BLNK: a central linker protein in B cell activation. | ACCEPT | Summary: Retain tyrosine kinase binding with the actual chicken SYK partner. Reason: The preserved partner F1N9Y5 is chicken SYK, as independently verified in Reactome and KEGG, not human SYK. The original source identifies BLNK as the link to BCR-associated SYK; the curated IPI association is coherent with this biochemistry. The exact species attribution is retained and no receptor-kinase activity is assigned to BLNK. Supporting Evidence: |
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Download this section (compressed HTML)Q: Does the ancestral RTK-signaling assertion at PTHR14098 PTN001019935 reflect a demonstrated BLNK receptor-tyrosine-kinase pathway distinct from its BCR role, and how does the experimental Clnk evidence support that node placement?
Q: Which exact BLNK domain/peptide pairs and affinity measurements underlie PMID:24728074 interactions with AR and KIT, and which BLNK peptide was used in the PMID:16969585 BTK SH2 study?
Q: How do the historical long/short SLP-65 constructs map onto the three current UniProt alternative products, and how do endogenous human BLNK granules compare with the reconstructed CIN85–vesicle condensates?
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