Vinculin (VCL) is a cytoplasmic actin-binding adaptor of the vinculin/alpha-catenin family that couples adhesion complexes to the actin cytoskeleton at both cell-matrix and cell-cell contacts. It has a helical-bundle head (domains D1-D4), a proline-rich hinge and a tail that binds actin filaments. In the resting molecule the head binds the tail and masks the F-actin site; binding of talin vinculin-binding sites (or of alpha-actinin, alpha-catenin, or bacterial talin mimics such as Shigella IpaA) to the D1 domain opens the molecule so that the tail can engage actin. At integrin-based focal adhesions, podosomes and muscle costameres, talin-activated vinculin reinforces the integrin-talin-actin linkage under actomyosin tension, regulates adhesion growth and turnover, and restrains cell migration; its hinge recruits the Arp2/3 complex and SH3-domain adaptors such as vinexin and CAP/ponsin. At cadherin-based adherens junctions it binds alpha-catenin and beta-catenin, stabilizes E-cadherin at the cell surface, and is needed for assembly of the apical junctional complex; in endothelium it shifts between focal adhesions and VE-cadherin junctions according to local tension. A muscle-specific splice isoform, metavinculin, carries a tail insert, and VCL variants cause dilated and hypertrophic cardiomyopathy. The vinculin/alpha-catenin family predates animals: a vinculin ortholog in the unicellular holozoan Capsaspora localizes with integrin in adhesive filopodia, and sponge vinculin binds talin and is activated by it for F-actin binding, indicating that talin-activated actin coupling at cell-substrate contacts is ancestral, whereas the catenin links to cadherin junctions are best documented in bilaterians.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002009 morphogenesis of an epithelium | IMP PMID:20086044 Vinculin regulates cell-surface E-cadherin expression by bin... | MARK AS OVER ANNOTATED | Summary: Vinculin knockdown/rescue in MCF10A mammary epithelial cells altered cell shape (loss of honeycomb morphology) and reduced cadherin-dependent adhesion by lowering surface E-cadherin. Reason: The phenotype is a change in cell morphology and cell-cell adhesion in a cultured monolayer, not morphogenesis of an epithelial tissue. The process the data support is captured by epithelial cell-cell adhesion and adherens junction assembly (both accepted from the same paper). Supporting Evidence: PMID:20086044 When this system was applied to epithelial cells, cell morphology was altered, and cadherin-dependent adhesion was reduced. |
| GO:0002102 podosome | IEA GO_REF:0000044 | ACCEPT | Summary: Vinculin is a component of the podosome adhesion ring (UniProt subcellular location, by similarity to mouse). Reason: Podosomes are integrin-based cell-matrix adhesions in which vinculin is a standard ring component; consistent with its role in cell-matrix adhesion. |
| GO:0002162 dystroglycan binding | IPI PMID:18341635 beta-Dystroglycan modulates the interplay between actin and ... | UNDECIDED | Summary: beta-dystroglycan was co-immunoprecipitated with focal adhesion proteins in adhered human platelets. Reason: Only the abstract is cached and it does not name vinculin as a direct dystroglycan partner; the platelet co-IP evidence cannot be inspected. A direct vinculin-dystroglycan interaction is not established elsewhere in the literature reviewed here. Supporting Evidence: PMID:18341635 beta-dystroglycan was found to act as an interplay protein between actin and microtubules |
| GO:0003779 actin binding | IDA PMID:16803572 Role of dystrophins and utrophins in platelet adhesion proce... | ACCEPT | Summary: Association of vinculin with actin in platelets (immunofluorescence/co-IP; abstract-only). Reason: Vinculin binds actin filaments through its tail domain; this is a core activity. The more precise term actin filament binding (GO:0051015) is proposed as a NEW row supported by fragment co-sedimentation and EM (PMID:7816144). Accepted here, deferring to the curator for the platelet-specific evidence. Supporting Evidence: PMID:7816144 Cosedimentation and crosslinking assays, and direct visualization by transmission electron microscopy, reveal an interaction between F-actin and a bacterially expressed fusion protein containing amino acids 811-1066 of vinculin |
| GO:0003779 actin binding | IDA NOT PMID:7816144 F-actin binding site masked by the intramolecular associatio... | REMOVE | Summary: NOT actin binding: intact purified vinculin does not co-sediment with or crosslink F-actin because the head-tail interaction masks the tail F-actin site. Reason: The same paper shows that the vinculin tail binds F-actin directly and that the site is cryptic, not absent, in the closed molecule. Activation by talin, alpha-actinin or pathogen VBS peptides exposes it, and actin binding is a core, conserved vinculin activity (also shown for sponge vinculin). A NOT annotation states that the gene product lacks the activity, which the paper itself contradicts; the autoinhibition is regulation, not absence of function. Supporting Evidence: PMID:7816144 Vinculin itself neither cosediments with nor crosslinks F-actin. PMID:7816144 an intramolecular association between the 95K head and 30K tail domains of vinculin masks an F-actin binding site present in the carboxy-terminal tail domain PMID:7816144 Cosedimentation and crosslinking assays, and direct visualization by transmission electron microscopy, reveal an interaction between F-actin and a bacterially expressed fusion protein containing amino acids 811-1066 of vinculin PMID:29880641 Thus, binding of talin to Op vinculin D1 releases autoinhibition for F-actin binding, similar to the behavior of vertebrate vinculin. |
| GO:0005198 structural molecule activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO mapping from the vinculin conserved-site signature (IPR000633) to structural molecule activity. Reason: Vinculin is not a structural constituent in the sense of a self-assembling scaffold. Its activity is to couple actin filaments to adhesion-complex proteins (talin at integrin adhesions, alpha-catenin/beta-catenin at cadherin junctions), which GO describes as cytoskeletal adaptor activity. Proposed replacements: cytoskeletal adaptor activity Supporting Evidence: PMID:29880641 VIN proteins link actin filaments to membrane proteins at the plasma membrane and are found in all animals and their close outgroups (choanoflagellates, chytridomycetes, apusozoa, amoebozoa) PMID:15070891 all of talin VBSs activate vinculin by provoking helical bundle conversion of the Vh domain, which displaces the vinculin tail (Vt) domain |
| GO:0005515 protein binding | IPI PMID:10320934 Integrin-mediated cell adhesion: the cytoskeletal connection... | MODIFY | Summary: IPI with TLN2, cited to a review on integrin-cytoskeleton linkage. Reason: The interaction is the talin-vinculin interaction (talin vinculin-binding sites bind the vinculin D1 head). Replace generic protein binding with talin binding. Proposed replacements: talin binding Supporting Evidence: PMID:10320934 Talin has two or more actin-binding sites, and three binding sites for the cytoskeletal protein vinculin. PMID:15070891 all of talin VBSs activate vinculin by provoking helical bundle conversion of the Vh domain, which displaces the vinculin tail (Vt) domain |
| GO:0005515 protein binding | IPI PMID:12473693 Recruitment of the Arp2/3 complex to vinculin: coupling memb... | MODIFY | Summary: Arp2/3 complex (ARPC2) binds directly to the vinculin hinge region. Reason: The paper shows direct, regulated binding of the Arp2/3 complex to vinculin; Arp2/3 complex binding is the informative term. Proposed replacements: Arp2/3 complex binding Supporting Evidence: PMID:12473693 Binding of the Arp2/3 complex to vinculin is direct and does not depend on the ability of vinculin to associate with actin. |
| GO:0005515 protein binding | IPI PMID:15070891 Structural basis for amplifying vinculin activation by talin... | MODIFY | Summary: Crystal structure of human vinculin head bound to talin VBS1 and biochemistry of talin VBSs. Reason: Talin binding to the vinculin D1 head is the central activating interaction. Replace generic protein binding with talin binding. Proposed replacements: talin binding Supporting Evidence: PMID:15070891 all of talin VBSs activate vinculin by provoking helical bundle conversion of the Vh domain, which displaces the vinculin tail (Vt) domain |
| GO:0005515 protein binding | IPI PMID:15163412 RNA and RNA binding proteins participate in early stages of ... | REMOVE | Summary: SILAC proteomics of attachment-dependent focal adhesion protein interactors (spreading initiation centers); partner RTCB. Reason: Generic protein binding is uninformative about function. Removal does not mean the reported interaction is false. This is a large-scale proteomic co-association with no specific functional implication for vinculin. |
| GO:0005515 protein binding | IPI PMID:15988023 Structural dynamics of alpha-actinin-vinculin interactions. | MODIFY | Summary: Structure of the alpha-actinin vinculin-binding helix (alphaVBS) bound to vinculin Vh1 (ACTN4). Reason: Direct structurally defined binding of alpha-actinin to vinculin D1; alpha-actinin binding is the informative term. Proposed replacements: alpha-actinin binding Supporting Evidence: PMID:15988023 alpha-Actinin interacts with vinculin through the binding of an alpha-helix (alphaVBS) present within the R4 spectrin repeat of its central rod domain to vinculin's N-terminal seven-helical bundle domain (Vh1) |
| GO:0005515 protein binding | IPI PMID:15988023 Structural dynamics of alpha-actinin-vinculin interactions. | MODIFY | Summary: Structure of the alpha-actinin vinculin-binding helix bound to vinculin Vh1 (ACTN1). Reason: As for ACTN4: direct alpha-actinin binding to vinculin D1. Proposed replacements: alpha-actinin binding Supporting Evidence: PMID:15988023 alpha-Actinin interacts with vinculin through the binding of an alpha-helix (alphaVBS) present within the R4 spectrin repeat of its central rod domain to vinculin's N-terminal seven-helical bundle domain (Vh1) |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | REMOVE | Summary: Yeast two-hybrid hit with ABI2 in a proteome-scale screen. Reason: Generic protein binding is uninformative about function. Removal does not mean the reported interaction is false. High-throughput Y2H without follow-up. |
| GO:0005515 protein binding | IPI PMID:16803572 Role of dystrophins and utrophins in platelet adhesion proce... | REMOVE | Summary: Association of dystrophin Dp71 complexes with focal adhesion proteins in platelets (co-IP; abstract-only). Reason: Generic protein binding is uninformative about function. Removal does not mean the reported interaction is false. Co-immunoprecipitation from platelets does not establish a direct or specific activity. Supporting Evidence: PMID:16803572 their potential association with integrin beta-1 fraction and the focal adhesion system (alpha-actinin, vinculin and talin) was evaluated by immunofluorescence and immunoprecipitation assays |
| GO:0005515 protein binding | IPI PMID:16803572 Role of dystrophins and utrophins in platelet adhesion proce... | REMOVE | Summary: Association of utrophin complexes with focal adhesion proteins in platelets (co-IP; abstract-only). Reason: Generic protein binding is uninformative about function. Removal does not mean the reported interaction is false. Co-immunoprecipitation from platelets does not establish a direct or specific activity. Supporting Evidence: PMID:16803572 their potential association with integrin beta-1 fraction and the focal adhesion system (alpha-actinin, vinculin and talin) was evaluated by immunofluorescence and immunoprecipitation assays |
| GO:0005515 protein binding | IPI PMID:17082770 CAP interacts with cytoskeletal proteins and regulates adhes... | MODIFY | Summary: CAP/ponsin (rat Sorbs1) binds vinculin through its first two SH3 domains and the vinculin proline-rich motifs. Reason: The paper maps the interface: CAP SH3 domains bind the proline-rich hinge of vinculin. SH3 domain binding is the informative MF. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:17082770 The interactions, which occur at cellβECM adhesions, require the first two SH3 domains of CAP and the proline-rich motifs of paxillin and vinculin. |
| GO:0005515 protein binding | IPI PMID:17932491 Vinculin binding in its closed conformation by a helix addit... | REMOVE | Summary: Shigella IpaA vinculin-binding site binds vinculin head domains (host-pathogen interaction). Reason: Generic protein binding is uninformative about function. Removal does not mean the reported interaction is false. The interaction is bacterial mimicry of talin; it is not a normal function of vinculin. Supporting Evidence: PMID:17932491 Talin, alpha-actinin, and the invasin IpaA of Shigella flexneri sever vinculin's head-tail interaction by inserting an alpha-helix into vinculin's N-terminal four-helical bundle |
| GO:0005515 protein binding | IPI PMID:18028034 Human alpha-synemin interacts directly with vinculin and met... | REMOVE | Summary: alpha-synemin SNTIII region binds vinculin and metavinculin. Reason: Generic protein binding is uninformative about function. Removal does not mean the reported interaction is false. No more specific MF term is justified from the abstract-only cache. Supporting Evidence: PMID:18028034 SNTIII interacts directly with both vinculin and metavinculin |
| GO:0005515 protein binding | IPI PMID:21525010 Novel vinculin binding site of the IpaA invasin of Shigella. | REMOVE | Summary: Third IpaA vinculin-binding site (IpaA-VBS3) binds and activates vinculin. Reason: Generic protein binding is uninformative about function. Removal does not mean the reported interaction is false. Host-pathogen talin mimicry. Supporting Evidence: PMID:21525010 one IpaA molecule can bind up to three vinculin molecules |
| GO:0005515 protein binding | IPI PMID:21841197 The rickettsia surface cell antigen 4 applies mimicry to bin... | REMOVE | Summary: Rickettsia Sca4 binds and activates vinculin via two VBSs. Reason: Generic protein binding is uninformative about function. Removal does not mean the reported interaction is false. Host-pathogen talin mimicry. Supporting Evidence: PMID:21841197 sca4 binds to and activates vinculin through two vinculin binding sites |
| GO:0005515 protein binding | IPI PMID:22427331 KIAA1797/FOCAD encodes a novel focal adhesion protein with t... | REMOVE | Summary: Focadhesin (FOCAD) co-immunoprecipitates with vinculin in glioma cells. Reason: Generic protein binding is uninformative about function. Removal does not mean the reported interaction is false. Co-IP only; no defined interface or activity. Supporting Evidence: PMID:22427331 Physical interaction between KIAA1797 and vinculin was demonstrated via co-immunoprecipitation. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Yeast two-hybrid hit with TEKT1 in the HuRI human interactome. Reason: Generic protein binding is uninformative about function. Removal does not mean the reported interaction is false. High-throughput Y2H with a ciliary/flagellar protein; no biological context. |
| GO:0005515 protein binding | IPI PMID:26923917 Dual role of vinculin in barrier-disruptive and barrier-enha... | REMOVE | Summary: VE-cadherin co-immunoprecipitates with vinculin in pulmonary endothelial cells; the association increases with OxPAPC and decreases with thrombin. Reason: Generic protein binding is uninformative about function. Removal does not mean the reported interaction is false. Vinculin reaches cadherins through alpha- and beta-catenin; co-IP does not show direct cadherin binding. The junctional role is captured by adherens junction and cell-cell junction rows. Supporting Evidence: PMID:26923917 In contrast, OxPAPC stimulated the vinculin association with VE-cadherin. |
| GO:0005515 protein binding | IPI PMID:26923917 Dual role of vinculin in barrier-disruptive and barrier-enha... | MODIFY | Summary: Talin co-immunoprecipitates with vinculin in thrombin-stimulated endothelial cells. Reason: Talin-vinculin association; replace generic protein binding with talin binding. Proposed replacements: talin binding Supporting Evidence: PMID:26923917 Thrombin stimulated the vinculin association with FA protein talin and suppressed the interaction with AJ protein, VE-cadherin. |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | REMOVE | Summary: ABI2 Y2H interaction from an interactome perturbation study. Reason: Generic protein binding is uninformative about function. Removal does not mean the reported interaction is false. High-throughput Y2H. |
| GO:0005515 protein binding | IPI PMID:9054445 Monocyte cells and cancer cells express novel paxillin isofo... | REMOVE | Summary: Paxillin gamma isoform co-precipitates with vinculin. Reason: Generic protein binding is uninformative about function. Removal does not mean the reported interaction is false. GO has no paxillin binding term (QuickGO search), and the co-precipitation does not define a more specific activity. Supporting Evidence: PMID:9054445 gamma bound to vinculin but only weakly to focal adhesion kinase |
| GO:0005515 protein binding | IPI PMID:9885244 Vinexin: a novel vinculin-binding protein with multiple SH3 ... | MODIFY | Summary: Vinexin (SORBS3) binds the vinculin proline-rich hinge through two SH3 domains (Y2H and in vitro binding). Reason: The interface is defined: vinexin SH3 domains bind the proline-rich region of vinculin. SH3 domain binding is the informative term. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:9885244 The interaction between vinexin and vinculin was mediated by two SH3 domains of vinexin and the proline-rich region of vinculin. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-482772 | MARK AS OVER ANNOTATED | Summary: Reactome TAS: extracellular region (platelet release / granule exocytosis reactions). Reason: Reactome places vinculin in this compartment because it was detected in platelet releasate or neutrophil granule proteomics. Vinculin is a cytoplasmic protein with no signal peptide whose function is at the cytoplasmic face of adhesions; any extracellular or granule-lumen presence is incidental release or contamination, not a site of function. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798748 | MARK AS OVER ANNOTATED | Summary: Reactome TAS: extracellular region (platelet release / granule exocytosis reactions). Reason: Reactome places vinculin in this compartment because it was detected in platelet releasate or neutrophil granule proteomics. Vinculin is a cytoplasmic protein with no signal peptide whose function is at the cytoplasmic face of adhesions; any extracellular or granule-lumen presence is incidental release or contamination, not a site of function. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798749 | MARK AS OVER ANNOTATED | Summary: Reactome TAS: extracellular region (platelet release / granule exocytosis reactions). Reason: Reactome places vinculin in this compartment because it was detected in platelet releasate or neutrophil granule proteomics. Vinculin is a cytoplasmic protein with no signal peptide whose function is at the cytoplasmic face of adhesions; any extracellular or granule-lumen presence is incidental release or contamination, not a site of function. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6800434 | MARK AS OVER ANNOTATED | Summary: Reactome TAS: extracellular region (platelet release / granule exocytosis reactions). Reason: Reactome places vinculin in this compartment because it was detected in platelet releasate or neutrophil granule proteomics. Vinculin is a cytoplasmic protein with no signal peptide whose function is at the cytoplasmic face of adhesions; any extracellular or granule-lumen presence is incidental release or contamination, not a site of function. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: cytoplasm (PANTHER node PTN005285701; human VCL among descendants). Reason: Vinculin is a cytoplasmic protein; correct at this general level. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-445699 | KEEP AS NON CORE | Summary: Reactome TAS: cytosol (smooth-muscle contraction, platelet, calpain cleavage, cadherin-catenin reactions). Reason: Inactive vinculin forms a soluble cytosolic pool, so the location is correct, but the functional pool is at the cytoplasmic face of focal adhesions and adherens junctions. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-445700 | KEEP AS NON CORE | Summary: Reactome TAS: cytosol (smooth-muscle contraction, platelet, calpain cleavage, cadherin-catenin reactions). Reason: Inactive vinculin forms a soluble cytosolic pool, so the location is correct, but the functional pool is at the cytoplasmic face of focal adhesions and adherens junctions. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-445704 | KEEP AS NON CORE | Summary: Reactome TAS: cytosol (smooth-muscle contraction, platelet, calpain cleavage, cadherin-catenin reactions). Reason: Inactive vinculin forms a soluble cytosolic pool, so the location is correct, but the functional pool is at the cytoplasmic face of focal adhesions and adherens junctions. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-445705 | KEEP AS NON CORE | Summary: Reactome TAS: cytosol (smooth-muscle contraction, platelet, calpain cleavage, cadherin-catenin reactions). Reason: Inactive vinculin forms a soluble cytosolic pool, so the location is correct, but the functional pool is at the cytoplasmic face of focal adhesions and adherens junctions. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-482772 | KEEP AS NON CORE | Summary: Reactome TAS: cytosol (smooth-muscle contraction, platelet, calpain cleavage, cadherin-catenin reactions). Reason: Inactive vinculin forms a soluble cytosolic pool, so the location is correct, but the functional pool is at the cytoplasmic face of focal adhesions and adherens junctions. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9861485 | KEEP AS NON CORE | Summary: Reactome TAS: cytosol (smooth-muscle contraction, platelet, calpain cleavage, cadherin-catenin reactions). Reason: Inactive vinculin forms a soluble cytosolic pool, so the location is correct, but the functional pool is at the cytoplasmic face of focal adhesions and adherens junctions. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9934294 | KEEP AS NON CORE | Summary: Reactome TAS: cytosol (smooth-muscle contraction, platelet, calpain cleavage, cadherin-catenin reactions). Reason: Inactive vinculin forms a soluble cytosolic pool, so the location is correct, but the functional pool is at the cytoplasmic face of focal adhesions and adherens junctions. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9934410 | KEEP AS NON CORE | Summary: Reactome TAS: cytosol (smooth-muscle contraction, platelet, calpain cleavage, cadherin-catenin reactions). Reason: Inactive vinculin forms a soluble cytosolic pool, so the location is correct, but the functional pool is at the cytoplasmic face of focal adhesions and adherens junctions. |
| GO:0005856 cytoskeleton | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: cytoskeleton. Reason: Vinculin is an actin-cytoskeleton-associated protein at adhesion sites. Supporting Evidence: PMID:2116004 a cytoskeletal protein associated with cell-cell and cell-matrix junctions |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | ACCEPT | Summary: IEA (UniProt SubCell): cytoskeleton. Reason: Correct; vinculin associates with the actin cytoskeleton. |
| GO:0005856 cytoskeleton | TAS PMID:16130169 Proteomics of human umbilical vein endothelial cells applied... | ACCEPT | Summary: TAS: cytoskeleton, from HUVEC proteomics (abstract-only). Reason: The location is correct for vinculin, though the source is a proteomic catalogue rather than a localization study. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: plasma membrane. Reason: Vinculin acts as a peripheral protein on the cytoplasmic face of the plasma membrane at adhesions. Supporting Evidence: PMID:15501673 Vinculin, a protein localized at the cytoplasmic face of cell-matrix and cell-cell adhesions, is required for strong cell adhesion. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA (UniProt SubCell): plasma membrane. Reason: Correct; peripheral membrane protein, cytoplasmic side. |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from chicken vinculin: plasma membrane. Reason: Correct; peripheral membrane protein at adhesion sites. |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse vinculin: plasma membrane. Reason: Correct; peripheral membrane protein at adhesion sites. |
| GO:0005911 cell-cell junction | IMP PMID:25753039 ZO-1 controls endothelial adherens junctions, cell-cell tens... | ACCEPT | Summary: Vinculin at endothelial cell-cell junctions redistributes to focal adhesions when ZO-1 is depleted. Reason: Directly shows vinculin at endothelial cell-cell junctions in a tension-dependent manner. Supporting Evidence: PMID:25753039 ZO-1 down-regulation triggered redistribution of vinculin from cellβcell junctions to focal adhesions |
| GO:0005911 cell-cell junction | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse vinculin: cell-cell junction. Reason: Consistent with experimental evidence for human vinculin at cell-cell junctions. Supporting Evidence: PMID:25753039 ZO-1 down-regulation triggered redistribution of vinculin from cellβcell junctions to focal adhesions |
| GO:0005912 adherens junction | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: adherens junction. Reason: Vinculin is a long-established adherens junction component; human VCL is among the experimental donors. Supporting Evidence: PMID:20086044 Vinculin, a well-known component of cell-matrix adhesions, is also present at the cytoplasmic domains of cadherins |
| GO:0005912 adherens junction | IDA PMID:20086044 Vinculin regulates cell-surface E-cadherin expression by bin... | ACCEPT | Summary: IDA: vinculin localizes to adherens junctions of MCF10A cells, dependent on beta-catenin binding. Reason: Direct localization in human epithelial cells. Supporting Evidence: PMID:20086044 Our experiments indicate a requirement of Ξ²-catenin for localization of vinculin to cell-cell junctions. |
| GO:0005912 adherens junction | IDA PMID:26923917 Dual role of vinculin in barrier-disruptive and barrier-enha... | ACCEPT | Summary: IDA: vinculin at VE-cadherin adherens junctions in pulmonary endothelial cells. Reason: Vinculin associates with VE-cadherin junctions, increased by barrier-enhancing OxPAPC. Supporting Evidence: PMID:26923917 In contrast, OxPAPC stimulated the vinculin association with VE-cadherin. |
| GO:0005912 adherens junction | IEA GO_REF:0000044 | ACCEPT | Summary: IEA (UniProt SubCell): adherens junction. Reason: Correct. |
| GO:0005912 adherens junction | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse vinculin: adherens junction. Reason: Correct. |
| GO:0005925 focal adhesion | HDA PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome... | ACCEPT | Summary: HDA: focal adhesion proteome (myosin II-responsive). Reason: Vinculin is a canonical focal adhesion protein enriched by myosin II tension. Supporting Evidence: PMID:21423176 We find that myosinII promotes enrichment of proteins that strengthen the integrin-actin linkage (migfilin, filamins, vinculin). |
| GO:0005925 focal adhesion | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: focal adhesion. Reason: Core location; human VCL is among the experimental donors (expected, not circular). |
| GO:0005925 focal adhesion | IDA GO_REF:0000052 | ACCEPT | Summary: IDA (Human Protein Atlas immunofluorescence): focal adhesion. Reason: Core location. |
| GO:0005925 focal adhesion | IDA PMID:15070891 Structural basis for amplifying vinculin activation by talin... | ACCEPT | Summary: IDA: focal adhesion (talin-vinculin structural paper). Reason: Core location; talin-vinculin interactions are essential at focal adhesions. Supporting Evidence: PMID:15070891 all of talin VBSs activate vinculin by provoking helical bundle conversion of the Vh domain, which displaces the vinculin tail (Vt) domain |
| GO:0005925 focal adhesion | IDA PMID:20086044 Vinculin regulates cell-surface E-cadherin expression by bin... | ACCEPT | Summary: IDA: focal adhesion in MCF10A cells. Reason: Core location; knockdown cells adhered normally to ECM in this study, consistent with a modulatory role. Supporting Evidence: PMID:20086044 despite adhering normally to the extracellular matrix |
| GO:0005925 focal adhesion | IDA PMID:29162887 The WD40-domain containing protein CORO2B is specifically en... | ACCEPT | Summary: IDA: vinculin used as a focal adhesion marker in human podocytes. Reason: Core location. Supporting Evidence: PMID:29162887 Immunofluorescence staining for F-ACTIN, VINCULIN and CORO2B-GFP in human immortalized podocytes reveals localization of CORO2B to ventral actin stress fibers and ventral focal adhesions. |
| GO:0005925 focal adhesion | IEA GO_REF:0000120 | ACCEPT | Summary: IEA (combined automated): focal adhesion. Reason: Core location. |
| GO:0005925 focal adhesion | IMP PMID:26923917 Dual role of vinculin in barrier-disruptive and barrier-enha... | ACCEPT | Summary: IMP: vinculin knockdown reduced focal adhesion size in thrombin-stimulated endothelial cells. Reason: Core location; the knockdown data also support regulation of focal adhesion assembly. Supporting Evidence: PMID:26923917 Vinculin knockdown significantly decreased the size of FA in thrombin-stimulated EC |
| GO:0005925 focal adhesion | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse vinculin: focal adhesion. Reason: Core location. |
| GO:0007155 cell adhesion | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: cell adhesion. Reason: Vinculin couples adhesion receptors (via talin and catenins) to actin and is required for strong adhesion; inherited across the vinculin/alpha-catenin family. Supporting Evidence: PMID:15501673 Vinculin, a protein localized at the cytoplasmic face of cell-matrix and cell-cell adhesions, is required for strong cell adhesion. |
| GO:0007155 cell adhesion | IEA GO_REF:0000002 | ACCEPT | Summary: IEA (InterPro2GO): cell adhesion. Reason: Correct at this general level. |
| GO:0007155 cell adhesion | TAS PMID:15501673 Vinculin--a dynamic regulator of cell adhesion. | ACCEPT | Summary: TAS: review on vinculin as a dynamic regulator of cell adhesion. Reason: Supported. Supporting Evidence: PMID:15501673 Vinculin, a protein localized at the cytoplasmic face of cell-matrix and cell-cell adhesions, is required for strong cell adhesion. |
| GO:0007160 cell-matrix adhesion | TAS PMID:20086044 Vinculin regulates cell-surface E-cadherin expression by bin... | ACCEPT | Summary: TAS: cell-matrix adhesion. Reason: Vinculin strengthens the integrin-talin-actin linkage at focal adhesions. In this particular study knockdown cells still adhered to ECM, so the role is reinforcement rather than absolute requirement; consistent with vinculin-null ES cells assembling focal adhesions. Supporting Evidence: PMID:20086044 Vinculin, a well-known component of cell-matrix adhesions, is also present at the cytoplasmic domains of cadherins PMID:21423176 We find that myosinII promotes enrichment of proteins that strengthen the integrin-actin linkage (migfilin, filamins, vinculin). PMID:10320934 whereas vinculin (-/-) ES cells are able to do so |
| GO:0008013 beta-catenin binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: beta-catenin binding (node PTN005285701; donors chicken vinculin and a Dictyostelium family member). Reason: Human vinculin binds the beta-catenin N-terminus (A50-dependent) experimentally, so the term is right for VCL. The node placement deserves scrutiny: a Dictyostelium donor suggests an alpha-catenin-type activity is being inherited, and sponge vinculin did not bind a beta-catenin peptide (although that peptide covered the alpha-catenin-binding region, not the N-terminal site vinculin uses). Supporting Evidence: PMID:20086044 the reduced surface E-cadherin expression could be rescued by introduction of vinculin, but not of a vinculin A50I substitution mutant that is defective for Ξ²-catenin binding PMID:29880641 Moreover, Op vinculin bound talin but not Ξ²-catenin |
| GO:0008013 beta-catenin binding | ISS PMID:20086044 Vinculin regulates cell-surface E-cadherin expression by bin... | ACCEPT | Summary: ISS from chicken vinculin, cited to Peng et al. 2010. Reason: Vinculin A50I, which cannot bind beta-catenin, fails to rescue surface E-cadherin. Supporting Evidence: PMID:20086044 the reduced surface E-cadherin expression could be rescued by introduction of vinculin, but not of a vinculin A50I substitution mutant that is defective for Ξ²-catenin binding |
| GO:0015629 actin cytoskeleton | IEA GO_REF:0000002 | ACCEPT | Summary: IEA (InterPro2GO): actin cytoskeleton. Reason: Correct. |
| GO:0016020 membrane | IEA GO_REF:0000117 | ACCEPT | Summary: IEA (ARBA): membrane. Reason: Correct but general; peripheral membrane protein. |
| GO:0030016 myofibril | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA (ARBA): myofibril. Reason: Vinculin/metavinculin sits at costameres and intercalated discs that link myofibrils to the sarcolemma; muscle-specific context. |
| GO:0030032 lamellipodium assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse: lamellipodium assembly. Reason: Vinculin recruits Arp2/3 to nascent adhesions and a hinge mutant reduces lamellipodial protrusion; real but secondary to its adhesion-actin coupling role. Supporting Evidence: PMID:12473693 Compared with WT vinculin, expression of this mutant in vinculin-null cells results in diminished lamellipodial protrusion and spreading on fibronectin. |
| GO:0030055 cell-substrate junction | NAS PMID:2116004 Complete sequence of human vinculin and assignment of the ge... | ACCEPT | Summary: NAS: cell-substrate junction (sequence paper). Reason: Correct; broader parent of focal adhesion. Supporting Evidence: PMID:2116004 a cytoskeletal protein associated with cell-cell and cell-matrix junctions |
| GO:0030336 negative regulation of cell migration | TAS PMID:15494027 Cytoskeletal proteins talin and vinculin in integrin-mediate... | KEEP AS NON CORE | Summary: TAS: negative regulation of cell migration (review). Reason: Vinculin regulates adhesion dynamics and migration (vinculin-null cells migrate faster); a downstream consequence of adhesion strengthening. Supporting Evidence: PMID:15494027 whereas vinculin appears to be important in regulating adhesion dynamics and cell migration |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:19725078 Proteomic analysis of increased Parkin expression and its in... | MARK AS OVER ANNOTATED | Summary: IPI: Parkin (PRKN) tandem affinity purification-MS interactor. Reason: Vinculin was one of 14 TAP-MS co-purifying proteins with Parkin, many of them abundant cytoskeletal or metabolic proteins. No functional ubiquitin ligase-binding role for vinculin is supported. Supporting Evidence: PMID:19725078 Tandem affinity purification/MS revealed 14 potential interactants of Parkin |
| GO:0032991 protein-containing complex | IDA PMID:9700171 alpha-Catenin-vinculin interaction functions to organize the... | KEEP AS NON CORE | Summary: IDA: protein-containing complex (alphaE-catenin/vinculin association). Reason: Correct but uninformative; the specific association is captured by alpha-catenin binding. Supporting Evidence: PMID:9700171 The 326-509 internal domain was found to bind vinculin. |
| GO:0034333 adherens junction assembly | IMP PMID:20086044 Vinculin regulates cell-surface E-cadherin expression by bin... | ACCEPT | Summary: IMP: adherens junction assembly (vinculin knockdown/rescue in MCF10A). Reason: Vinculin binding to beta-catenin is needed for surface E-cadherin and normal cell-cell junctions; vinculin is itself a junctional component that links the cadherin-catenin complex to actin. Supporting Evidence: PMID:20086044 Thus, vinculin regulates cell-surface E-cadherin expression by binding to Ξ²-catenin. PMID:20086044 The vinculin knockdown cells we generated are characterized by altered cell-cell adhesions |
| GO:0034394 protein localization to cell surface | IMP PMID:20086044 Vinculin regulates cell-surface E-cadherin expression by bin... | KEEP AS NON CORE | Summary: IMP: protein localization to cell surface (E-cadherin). Reason: Vinculin knockdown lowers surface E-cadherin without changing total levels. This is the mechanism by which vinculin supports junctions (stabilizing cadherin complexes), not a trafficking role. Supporting Evidence: PMID:20086044 Thus, vinculin regulates cell-surface E-cadherin expression by binding to Ξ²-catenin. |
| GO:0034774 secretory granule lumen | TAS Reactome:R-HSA-6798748 | MARK AS OVER ANNOTATED | Summary: Reactome TAS: granule lumen (neutrophil/secretory granule exocytosis reactions). Reason: Reactome places vinculin in this compartment because it was detected in platelet releasate or neutrophil granule proteomics. Vinculin is a cytoplasmic protein with no signal peptide whose function is at the cytoplasmic face of adhesions; any extracellular or granule-lumen presence is incidental release or contamination, not a site of function. |
| GO:0035580 specific granule lumen | TAS Reactome:R-HSA-6798749 | MARK AS OVER ANNOTATED | Summary: Reactome TAS: granule lumen (neutrophil/secretory granule exocytosis reactions). Reason: Reactome places vinculin in this compartment because it was detected in platelet releasate or neutrophil granule proteomics. Vinculin is a cytoplasmic protein with no signal peptide whose function is at the cytoplasmic face of adhesions; any extracellular or granule-lumen presence is incidental release or contamination, not a site of function. |
| GO:0035633 maintenance of blood-brain barrier | NAS PMID:30280653 Blood-Brain Barrier: From Physiology to Disease and Back. | MARK AS OVER ANNOTATED | Summary: NAS: maintenance of blood-brain barrier, cited to a BBB review. Reason: The cached full text of this review does not mention vinculin. Vinculin acts at endothelial junctions generally, but a tissue-level BBB maintenance role is not supported by the cited source. |
| GO:0042383 sarcolemma | IEA GO_REF:0000044 | ACCEPT | Summary: IEA (UniProt SubCell): sarcolemma. Reason: Vinculin/metavinculin are costameric sarcolemmal proteins in muscle. |
| GO:0042383 sarcolemma | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse: sarcolemma. Reason: Correct for muscle. |
| GO:0043034 costamere | IDA PMID:9415431 Spatial and temporal expression of the beta1D integrin durin... | ACCEPT | Summary: IDA: costamere (study of integrin beta1D localization in muscle; abstract-only). Reason: Vinculin is a classic costamere marker; the abstract describes beta1D at costameres and the curator presumably used vinculin co-staining in the full text. Supporting Evidence: PMID:9415431 In adults there is a distinct concentration of beta1D at the myotendinous junctions of muscle fibers and at costameres in both cardiac and skeletal muscle. |
| GO:0043034 costamere | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse: costamere. Reason: Correct for striated muscle. |
| GO:0043297 apical junction assembly | IMP PMID:9700171 alpha-Catenin-vinculin interaction functions to organize the... | ACCEPT | Summary: IMP: apical junction assembly (vinculin-null F9 cells, rescued by vinculin re-expression). Reason: The alphaE-catenin-vinculin interaction organizes the apical junctional complex; vinculin-null cells fail to form continuous ZO-1 networks. Supporting Evidence: PMID:9700171 In vinculin-null F9 cells, their apical junctional organization was impaired, and this phenotype was rescued by reexpression of vinculin. PMID:9700171 These results indicate that the alphaE-catenin-vinculin interaction plays a role in the assembly of the apical junctional complex in epithelia. |
| GO:0044291 cell-cell contact zone | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: cell-cell contact zone. Reason: Includes intercalated discs and junctional zones where vinculin resides. |
| GO:0044291 cell-cell contact zone | IEA GO_REF:0000117 | ACCEPT | Summary: IEA (ARBA): cell-cell contact zone. Reason: Correct. |
| GO:0044291 cell-cell contact zone | IMP PMID:26923917 Dual role of vinculin in barrier-disruptive and barrier-enha... | ACCEPT | Summary: IMP: cell-cell contact zone (endothelial). Reason: Vinculin knockdown reduced VE-cadherin-positive junctional areas. Supporting Evidence: PMID:26923917 Vinculin knockdown significantly reduced the enlargement of VE-cadherin positive areas |
| GO:0045294 alpha-catenin binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: alpha-catenin binding. Reason: Vinculin binds the alphaE-catenin internal domain; human VCL is among the experimental donors. Supporting Evidence: PMID:9700171 The 326-509 internal domain was found to bind vinculin. |
| GO:0045294 alpha-catenin binding | IPI PMID:9700171 alpha-Catenin-vinculin interaction functions to organize the... | ACCEPT | Summary: IPI: alphaE-catenin residues 326-509 bind vinculin. Reason: Direct binding mapped to the alpha-catenin vinculin-binding domain. Supporting Evidence: PMID:9700171 The 326-509 internal domain was found to bind vinculin. |
| GO:0045296 cadherin binding | HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | MARK AS OVER ANNOTATED | Summary: HDA: E-cadherin proximity/affinity interactome (cadhesome). Reason: Vinculin is recruited to cadherin complexes through alpha-catenin and beta-catenin. Detection in an E-cadherin interactome does not show direct cadherin binding; the specific interactions are captured by alpha-catenin binding and beta-catenin binding. Supporting Evidence: PMID:25468996 While a number of proteins, most notably Ξ±-catenin, vinculin, and eplin, have been implicated in cadherin mechanotransduction PMID:20086044 Vinculin, a well-known component of cell-matrix adhesions, is also present at the cytoplasmic domains of cadherins |
| GO:0045296 cadherin binding | ISS PMID:20086044 Vinculin regulates cell-surface E-cadherin expression by bin... | MARK AS OVER ANNOTATED | Summary: ISS from chicken vinculin, cited to Peng et al. 2010: cadherin binding. Reason: The cited study shows vinculin binds beta-catenin, which links it to E-cadherin; it does not show binding to the cadherin itself. Supporting Evidence: PMID:20086044 the reduced surface E-cadherin expression could be rescued by introduction of vinculin, but not of a vinculin A50I substitution mutant that is defective for Ξ²-catenin binding |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: IEA (UniProt SubCell): perinuclear region of cytoplasm. Reason: Reported by similarity to mouse; not a site of core function. |
| GO:0048471 perinuclear region of cytoplasm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse: perinuclear region of cytoplasm. Reason: Not a site of core function. |
| GO:0051893 regulation of focal adhesion assembly | IMP PMID:26923917 Dual role of vinculin in barrier-disruptive and barrier-enha... | ACCEPT | Summary: IMP: vinculin knockdown reduced thrombin-induced focal adhesion enlargement in endothelial cells. Reason: Vinculin regulates focal adhesion growth and maturation under tension rather than initial assembly. Supporting Evidence: PMID:26923917 Vinculin knockdown significantly decreased the size of FA in thrombin-stimulated EC |
| GO:0051893 regulation of focal adhesion assembly | NAS PMID:15070891 Structural basis for amplifying vinculin activation by talin... | ACCEPT | Summary: NAS: regulation of focal adhesion assembly (talin-vinculin structure paper). Reason: Talin activation of vinculin is proposed to drive actin reorganization at focal adhesions. Supporting Evidence: PMID:15070891 all of talin VBSs activate vinculin by provoking helical bundle conversion of the Vh domain, which displaces the vinculin tail (Vt) domain |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: HDA: urinary exosome proteomics. Reason: High-throughput detection in exosomes; not a functional location. |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: HDA: B-cell exosome proteomics. Reason: High-throughput detection in exosomes; not a functional location. |
| GO:0070527 platelet aggregation | HMP PMID:23382103 Platelet proteome analysis reveals integrin-dependent aggreg... | MARK AS OVER ANNOTATED | Summary: HMP: reduced vinculin among many proteins in platelets from myelodysplastic syndrome patients with aggregation defects. Reason: The data are correlative: vinculin is one of many proteins at lower levels in MDS platelets, and the paper attributes the integrin activation defect mainly to talin-1 and kindlin-3. Vinculin is discussed in relation to platelet spreading, not shown to be required for aggregation. Supporting Evidence: PMID:23382103 Besides activation of integrin Ξ± IIb Ξ² 3 , the ability to spread on immobilized fibrinogen requires the presence of Vinculin |
| GO:0090136 epithelial cell-cell adhesion | IMP PMID:20086044 Vinculin regulates cell-surface E-cadherin expression by bin... | ACCEPT | Summary: IMP: epithelial cell-cell adhesion (vinculin knockdown/rescue in MCF10A). Reason: Vinculin knockdown reduced cadherin-dependent adhesion, rescued by wild-type but not beta-catenin-binding-defective vinculin. Supporting Evidence: PMID:20086044 When this system was applied to epithelial cells, cell morphology was altered, and cadherin-dependent adhesion was reduced. PMID:20086044 the reduced surface E-cadherin expression could be rescued by introduction of vinculin, but not of a vinculin A50I substitution mutant that is defective for Ξ²-catenin binding |
| GO:1903140 regulation of establishment of endothelial barrier | IDA PMID:26923917 Dual role of vinculin in barrier-disruptive and barrier-enha... | KEEP AS NON CORE | Summary: IDA: vinculin knockdown blunted both thrombin-induced permeability increase and OxPAPC-induced barrier enhancement. Reason: A tissue-context consequence of vinculin coupling focal adhesions and adherens junctions to actomyosin in endothelium. Supporting Evidence: PMID:26923917 Knockdown of vinculin attenuated both, OxPAPC-induced decrease and thrombin-induced increase in EC permeability. |
| GO:1903561 extracellular vesicle | HDA PMID:24769233 Proteomic analysis of cerebrospinal fluid extracellular vesi... | KEEP AS NON CORE | Summary: HDA: cerebrospinal fluid extracellular vesicle proteomics. Reason: High-throughput detection; not a functional location. |
| GO:1904702 regulation of protein localization to adherens junction | IMP PMID:26923917 Dual role of vinculin in barrier-disruptive and barrier-enha... | KEEP AS NON CORE | Summary: IMP: vinculin knockdown reduced OxPAPC-induced enlargement of VE-cadherin junctions. Reason: Consistent with vinculin reinforcing adherens junctions under tension; endothelial context. Supporting Evidence: PMID:26923917 Vinculin knockdown significantly reduced the enlargement of VE-cadherin positive areas |
| GO:1904813 ficolin-1-rich granule lumen | TAS Reactome:R-HSA-6800434 | MARK AS OVER ANNOTATED | Summary: Reactome TAS: granule lumen (neutrophil/secretory granule exocytosis reactions). Reason: Reactome places vinculin in this compartment because it was detected in platelet releasate or neutrophil granule proteomics. Vinculin is a cytoplasmic protein with no signal peptide whose function is at the cytoplasmic face of adhesions; any extracellular or granule-lumen presence is incidental release or contamination, not a site of function. |
| GO:0051015 actin filament binding | IDA PMID:7816144 F-actin binding site masked by the intramolecular associatio... | NEW | Summary: Vinculin tail domain (residues 811-1066 and 858-1066) binds F-actin directly (co-sedimentation, crosslinking, EM); the site is masked by the head in the closed molecule and exposed by talin binding. Reason: GOA has only the generic actin binding term (plus a NOT row reflecting autoinhibition). Actin filament binding is the precise, core activity of vinculin, conserved to sponge vinculin where talin peptide releases F-actin binding. Supporting Evidence: PMID:7816144 Cosedimentation and crosslinking assays, and direct visualization by transmission electron microscopy, reveal an interaction between F-actin and a bacterially expressed fusion protein containing amino acids 811-1066 of vinculin PMID:7816144 an intramolecular association between the 95K head and 30K tail domains of vinculin masks an F-actin binding site present in the carboxy-terminal tail domain PMID:29880641 Thus, binding of talin to Op vinculin D1 releases autoinhibition for F-actin binding, similar to the behavior of vertebrate vinculin. |
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Download this section (compressed HTML)Q: Is vinculin binding to beta-catenin ancestral or a bilaterian innovation? Sponge vinculin did not bind a beta-catenin peptide, but that peptide covered the alpha-catenin-binding region rather than the beta-catenin N-terminus that human vinculin uses (A50/M8P interface). Does sponge or Capsaspora vinculin bind full-length beta-catenin of its own species?
Q: Is the beta-catenin binding IBA at PANTHER node PTN005285701 placed too deep? Donors include a Dictyostelium vinculin/alpha-catenin family member, whose beta-catenin (Aardvark) binding is an alpha-catenin-type activity; should the vinculin clade inherit it?
Q: Does Capsaspora vinculin bind Capsaspora talin and become activated for F-actin binding, as sponge vinculin does, and does it reach integrin beta2 through talin in filopodial adhesions?
Q: Should GO have a term for paxillin binding, given the well-characterized vinculin-paxillin interaction and its use across the integrin adhesome?
Experiment: Measure binding of recombinant Capsaspora and choanoflagellate vinculins to their own talin VBS peptides, alpha-catenin and full-length beta-catenin (ITC or pull-down), and test talin-dependent F-actin co-sedimentation, to map which interfaces predate animals.
Type: Binding assay
Experiment: Knock out or knock down vinculin in Capsaspora and score filopodial substrate adhesion, integrin beta2 patch formation and aggregation, to test whether the ancestral role is substrate adhesion.
Type: Genetic perturbation
Experiment: In vinculin-null human epithelial cells, rescue with human vinculin carrying swapped sponge or Capsaspora D1 domains and score E-cadherin surface levels and apical junction assembly, to test whether premetazoan vinculin heads can support cadherin-junction function.
Type: Structure-function rescue
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