Talin-1 is a large (about 270 kDa) cytoplasmic adaptor protein that links integrin adhesion receptors to the actin cytoskeleton. Its N-terminal FERM head binds the membrane-proximal NPxY motif of integrin beta cytoplasmic tails and acidic phospholipids, notably PI(4,5)P2; head binding to the integrin tail, together with kindlins, is a final step of inside-out integrin activation. The long rod of helical bundles carries cryptic vinculin-binding sites that are exposed under mechanical force and recruit and activate vinculin, and the rod and C-terminal I/LWEQ domain bind actin filaments, so talin acts as a mechanosensitive scaffold at focal adhesions. Talin-1 is widely expressed, is concentrated at focal adhesions and membrane ruffles, and keeps an autoinhibited cytosolic pool. It is required for assembly of integrin-matrix adhesions and, in platelets and leukocytes, for integrin activation underlying platelet aggregation and immune cell adhesion. Talin is older than animals: homologs are present in amoebozoans and in unicellular holozoans such as Capsaspora, whose integrin beta tails retain the NPxY motif, and a sponge talin vinculin-binding peptide activates sponge vinculin, so the integrin-talin-vinculin link was in place in the earliest animals.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001726 ruffle | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Ruffle localization by InterPro mapping from the talin central domain. UniProt records talin at membrane ruffles, where it colocalizes with LAYN. Reason: Talin is recruited to the leading edge and membrane ruffles of migrating cells, consistent with its role in nascent integrin adhesions, but ruffles are a secondary site relative to focal adhesions. Supporting Evidence: PMID:11279249 Talin is a major link between integrin and the actin cytoskeleton and was shown to play an important role in focal adhesion assembly. |
| GO:0001726 ruffle | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ruffle localization by ISS transfer from chicken talin (P54939). UniProt records talin at membrane ruffles, where it colocalizes with LAYN. Reason: Talin is recruited to the leading edge and membrane ruffles of migrating cells, consistent with its role in nascent integrin adhesions, but ruffles are a secondary site relative to focal adhesions. Supporting Evidence: PMID:11279249 Talin is a major link between integrin and the actin cytoskeleton and was shown to play an important role in focal adhesion assembly. |
| GO:0001786 phosphatidylserine binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara transfer of phosphatidylserine binding from mouse talin-1. Reason: The talin FERM head binds acidic membrane phospholipids, which helps it engage the inner leaflet of the plasma membrane before integrin binding. The best-characterized lipid partner is PI(4,5)P2; phosphatidylserine binding is plausible but a supporting rather than core activity. Supporting Evidence: PMID:11279249 the interaction between integrin and talin was greatly enhanced by PI4,5P(2)-induced talin activation |
| GO:0003779 actin binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro mapping (I/LWEQ and talin domains) to actin binding. Reason: Talin binds F-actin through its rod and the C-terminal I/LWEQ (THATCH) domain, forming the actin end of the integrin-actin link. The more specific actin filament binding is also annotated. Supporting Evidence: PMID:11279249 Talin is a major link between integrin and the actin cytoskeleton and was shown to play an important role in focal adhesion assembly. |
| GO:0005178 integrin binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from the talin family node PTN001072688; human TLN1 is among the experimental sources, as expected. Reason: Binding of the talin FERM head (F3 PTB-like subdomain) to the membrane-proximal NPxY motif of integrin beta cytoplasmic tails is the defining activity of talin and is required for integrin activation. The NPxY motif is conserved even in integrin beta subunits of Capsaspora, so this interaction can be inherited. Supporting Evidence: PMID:16546176 Talin mediates integrin signaling by binding to integrin cytoplasmic tails through its FERM domain PMID:11279249 the interaction between integrin and talin was greatly enhanced by PI4,5P(2)-induced talin activation PMID:35044719 Talinβ1 (TLN1) is a cytoplasmic adapter protein necessary for integrinβmediated cell adhesion |
| GO:0005178 integrin binding | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer from mouse talin-1. Reason: Binding of the talin FERM head (F3 PTB-like subdomain) to the membrane-proximal NPxY motif of integrin beta cytoplasmic tails is the defining activity of talin and is required for integrin activation. The NPxY motif is conserved even in integrin beta subunits of Capsaspora, so this interaction can be inherited. Supporting Evidence: PMID:16546176 Talin mediates integrin signaling by binding to integrin cytoplasmic tails through its FERM domain PMID:11279249 the interaction between integrin and talin was greatly enhanced by PI4,5P(2)-induced talin activation PMID:35044719 Talinβ1 (TLN1) is a cytoplasmic adapter protein necessary for integrinβmediated cell adhesion |
| GO:0005178 integrin binding | IPI PMID:12473654 Disruption of focal adhesions by integrin cytoplasmic domain... | ACCEPT | Summary: IPI with ITGB1 (P05556); ICAP-1alpha competes with talin for the beta1A integrin tail. Reason: Direct talin-beta1 integrin tail binding is well established; the cited abstract states that ICAP-1alpha inhibits the association of beta1A integrin with talin. Supporting Evidence: PMID:12473654 inhibit the association of beta(1A) integrin with talin, which is crucial for the assembly of these structures |
| GO:0005200 structural constituent of cytoskeleton | IEA GO_REF:0000002 | MODIFY | Summary: InterPro mapping from the talin central domain (IPR015224) to structural constituent of cytoskeleton. Reason: Talin is not a polymer-forming structural subunit of the cytoskeleton. It is a large adaptor that links integrin tails and membrane lipids (FERM head) to actin filaments and vinculin (rod), i.e. it brings a cytoskeletal polymer together with membrane receptors. Cytoskeletal adaptor activity describes this better. Proposed replacements: cytoskeletal adaptor activity Supporting Evidence: PMID:11279249 Talin is a major link between integrin and the actin cytoskeleton and was shown to play an important role in focal adhesion assembly. PMID:15494027 The cytoskeletal proteins talin and vinculin form part of a macromolecular complex on the cytoplasmic face of integrin-mediated cellular junctions with the extracellular matrix. |
| GO:0005515 protein binding | IPI PMID:11279249 Conformation, localization, and integrin binding of talin de... | MODIFY | Summary: IPI with ITGB1 (P05556) in a study of phosphoinositide-dependent talin activation. Reason: Generic protein binding is uninformative; the partner is the beta1 integrin cytoplasmic tail, and the paper shows PI(4,5)P2 enhances integrin binding by talin. Replace with integrin binding. Proposed replacements: integrin binding Supporting Evidence: PMID:11279249 the interaction between integrin and talin was greatly enhanced by PI4,5P(2)-induced talin activation |
| GO:0005515 protein binding | IPI PMID:16273093 A quantitative protein interaction network for the ErbB rece... | REMOVE | Summary: IPI with EGFR (P00533) from a protein-microarray screen of SH2/PTB domains against ErbB phosphopeptides. Reason: High-throughput in vitro measurement of a talin PTB-like domain against receptor phosphopeptides; the talin F3 domain does not favour phosphorylated NPxY motifs and no physiological role is shown. Generic protein binding is uninformative; removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:16273093 A quantitative protein interaction network for the ErbB rece... | REMOVE | Summary: IPI with ERBB2 (P04626) from a protein-microarray screen of SH2/PTB domains against ErbB phosphopeptides. Reason: High-throughput in vitro measurement of a talin PTB-like domain against receptor phosphopeptides; the talin F3 domain does not favour phosphorylated NPxY motifs and no physiological role is shown. Generic protein binding is uninformative; removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:16546176 TA205, an anti-talin monoclonal antibody, inhibits integrin-... | MODIFY | Summary: IPI with ITGB3 (P05106); the TA205 antibody allosterically inhibits alphaIIb beta3 binding to the talin FERM domain. Reason: The interaction is talin FERM binding to integrin beta3 tails; integrin binding is the informative term. Proposed replacements: integrin binding Supporting Evidence: PMID:16546176 Talin mediates integrin signaling by binding to integrin cytoplasmic tails through its FERM domain |
| GO:0005515 protein binding | IPI PMID:18342854 Identification of a repeated domain within mammalian alpha-s... | REMOVE | Summary: IPI with alpha-synemin (O15061); the SNTIII insert of alpha-synemin binds the talin rod. Reason: Generic protein binding is uninformative. The interaction links intermediate filaments to costameres in muscle; it does not define a specific talin molecular function beyond adaptor activity already captured. Removal does not mean the interaction is false. Supporting Evidence: PMID:18342854 binds to the rod domain of talin in vitro and co-localizes with talin at focal adhesion sites |
| GO:0005515 protein binding | IPI PMID:19608030 ANKRD1, the gene encoding cardiac ankyrin repeat protein, is... | REMOVE | Summary: IPI with ANKRD1/CARP (Q15327) from yeast two-hybrid in a cardiomyopathy study. Reason: Generic protein binding is uninformative; the yeast two-hybrid interaction lost in cardiomyopathy CARP variants does not establish a specific talin activity. Removal does not mean the interaction is false. Supporting Evidence: PMID:19608030 Both the P105S and M184I substitutions result in loss of CARP binding with Talin 1. |
| GO:0005515 protein binding | IPI PMID:26923917 Dual role of vinculin in barrier-disruptive and barrier-enha... | MODIFY | Summary: IPI with vinculin (P18206) by co-immunoprecipitation in human pulmonary endothelial cells. Reason: The partner is vinculin; thrombin increased vinculin-talin association. Vinculin binding is the informative term and is a core talin activity. Proposed replacements: vinculin binding Supporting Evidence: PMID:26923917 Thrombin treatment significantly increased the vinculin association with FA partner talin |
| GO:0005515 protein binding | IPI PMID:27895300 THSD1 (Thrombospondin Type 1 Domain Containing Protein 1) Mu... | REMOVE | Summary: IPI with THSD1 (Q9NS62); THSD1 forms a complex with FAK, talin and vinculin (UniProt SUBUNIT). Reason: Generic protein binding is uninformative; the cached abstract does not describe the talin interaction and no specific talin activity follows from it. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:32203420 Systems analysis of RhoGEF and RhoGAP regulatory proteins re... | REMOVE | Summary: IPI with ARHGAP31 (Q2M1Z3) from a systems-level RhoGEF/RhoGAP interactome. Reason: High-throughput interactome result; generic protein binding is uninformative and no specific talin activity follows. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:35044719 Proteome-scale mapping of binding sites in the unstructured ... | REMOVE | Summary: IPI with PIP5K1C (O60331) by proteomic peptide-phage display against the talin PTB-like domain. Reason: The PIP5K1C-talin interaction targets the kinase to focal adhesions and is biologically real, but generic protein binding conveys no function; a peptide-phage display hit alone does not support a more specific MF term. Removal does not mean the interaction is false. Supporting Evidence: PMID:35044719 Talinβ1 (TLN1) is a cytoplasmic adapter protein necessary for integrinβmediated cell adhesion |
| GO:0005515 protein binding | IPI PMID:35044719 Proteome-scale mapping of binding sites in the unstructured ... | MODIFY | Summary: IPI with ITGB3 (P05106) by peptide-phage display; the integrin beta3 NPxY peptide was a known TLN1 PTB ligand included in the screen. Reason: Partner is the integrin beta3 tail; integrin binding is the informative term. Proposed replacements: integrin binding Supporting Evidence: PMID:35044719 Talinβ1 (TLN1) is a cytoplasmic adapter protein necessary for integrinβmediated cell adhesion |
| GO:0005515 protein binding | IPI PMID:35044719 Proteome-scale mapping of binding sites in the unstructured ... | REMOVE | Summary: IPI with RET (P07949) by peptide-phage display. Reason: Proteome-scale phage display hit; generic protein binding is uninformative and a physiological role is not established. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:35044719 Proteome-scale mapping of binding sites in the unstructured ... | REMOVE | Summary: IPI with ARHGAP31 (Q2M1Z3) by peptide-phage display. Reason: Proteome-scale phage display hit; generic protein binding is uninformative. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:39009827 Proteome-scale characterisation of motif-based interactome r... | REMOVE | Summary: IPI with RET (P07949); a TLN1/TLN2 PTB-binding site in RET is disrupted by disease mutations. Reason: Phage display and validation of a PTB-RET peptide interaction; the authors only suggest TLN1 might be implicated in RET signalling. Generic protein binding is uninformative. Removal does not mean the interaction is false. Supporting Evidence: PMID:39009827 we highlight a talin 1 and 2 (TLN1 and TLN2) PTB binding site in the proto-oncogene tyrosine-protein kinase receptor Ret (RET) |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-482772 | MARK AS OVER ANNOTATED | Summary: Reactome TAS: talin among cytosolic components released by activated platelets. Reason: Talin is an intracellular cytoskeletal protein. Its appearance in the platelet releasate reflects platelet content release, not a function performed in the extracellular region. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: IBA cytoplasm from PTN000463398; human TLN1 is one of the experimental sources. Reason: Talin is a cytoplasmic protein, present in an autoinhibited cytosolic pool and recruited to the cytoplasmic face of the plasma membrane at adhesions. Supporting Evidence: PMID:15494027 The cytoskeletal proteins talin and vinculin form part of a macromolecular complex on the cytoplasmic face of integrin-mediated cellular junctions with the extracellular matrix. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence: cytosol. Reason: Consistent with the cytosolic autoinhibited pool of talin. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1791137 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-1791137), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-354066 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-354066), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-354073 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-354073), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-354077 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-354077), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-354087 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-354087), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-354097 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-354097), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-354124 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-354124), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-354149 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-354149), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-354165 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-354165), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-372693 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-372693), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-372697 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-372697), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-372705 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-372705), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-377640 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-377640), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-377641 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-377641), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-377643 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-377643), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-377644 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-377644), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-399936 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-399936), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-429415 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-429415), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-429441 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-429441), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-432096 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-432096), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-443905 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-443905), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-443910 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-443910), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-445699 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-445699), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-445700 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-445700), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-445704 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-445704), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-445705 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-445705), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-482772 | ACCEPT | Summary: Reactome TAS cytosol (Reactome:R-HSA-482772), from integrin alphaIIb beta3 signalling, talin activation or platelet reactions. Reason: Talin acts at the cytoplasmic face of the plasma membrane and has a cytosolic pool; the cytosol location is correct though generic. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell mapping to cytoskeleton. Reason: Talin is an actin-associated cytoskeletal protein concentrated at focal adhesions. Supporting Evidence: PMID:15494027 The cytoskeletal proteins talin and vinculin form part of a macromolecular complex on the cytoplasmic face of integrin-mediated cellular junctions with the extracellular matrix. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IBA plasma membrane from PTN000463398; human TLN1 is among the experimental sources. Reason: Talin binds PI(4,5)P2 and integrin tails at the cytoplasmic face of the plasma membrane; PI(4,5)P2 is necessary for its membrane localization. Supporting Evidence: PMID:11279249 the interaction between integrin and talin was greatly enhanced by PI4,5P(2)-induced talin activation |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence: plasma membrane. Reason: Consistent with recruitment of talin to the inner face of the plasma membrane. Supporting Evidence: PMID:11279249 the interaction between integrin and talin was greatly enhanced by PI4,5P(2)-induced talin activation |
| GO:0005912 adherens junction | IMP PMID:26923917 Dual role of vinculin in barrier-disruptive and barrier-enha... | MARK AS OVER ANNOTATED | Summary: IMP adherens junction from a study of vinculin in endothelial barrier function. Reason: The full text shows talin used as a focal adhesion marker and as the focal adhesion partner of vinculin; at the cell periphery after OxPAPC the authors interpret the colocalization as increased vinculin presence at adherens junctions. Talin is a component of integrin-matrix adhesions, and adherens junctions are built on cadherins and catenins. The evidence supports vinculin, not talin, at adherens junctions. Supporting Evidence: PMID:26923917 OxPAPC stimulation promoted vinculin-VE-cadherin and vinculin-talin colocalization at the cell periphery suggesting an increased vinculin presence at AJ PMID:26923917 Thrombin treatment significantly increased the vinculin association with FA partner talin PMID:29880641 The AJ (containing cadherins and catenins) and FAs (comprising integrins, talin, and paxillin) differ in protein composition |
| GO:0005925 focal adhesion | HDA PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome... | ACCEPT | Summary: HDA: talin-1 is part of the myosin-II-responsive focal adhesion proteome. Reason: Talin is a core structural component of focal adhesions, linking integrins to actin; this is its principal location. Supporting Evidence: PMID:21423176 Blebbistatin also weakly inhibited FA abundance of talin-1 (MDR:1.33) and vinculin (MDR:1.41) |
| GO:0005925 focal adhesion | IBA GO_REF:0000033 | ACCEPT | Summary: IBA focal adhesion from talin node PTN001072690. Reason: Talin is a core structural component of focal adhesions, linking integrins to actin; this is its principal location. Supporting Evidence: PMID:15494027 The cytoskeletal proteins talin and vinculin form part of a macromolecular complex on the cytoplasmic face of integrin-mediated cellular junctions with the extracellular matrix. |
| GO:0005925 focal adhesion | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence: focal adhesions. Reason: Talin is a core structural component of focal adhesions, linking integrins to actin; this is its principal location. Supporting Evidence: PMID:11279249 Talin is a major link between integrin and the actin cytoskeleton and was shown to play an important role in focal adhesion assembly. |
| GO:0005925 focal adhesion | IDA PMID:15070891 Structural basis for amplifying vinculin activation by talin... | ACCEPT | Summary: IDA focal adhesion from a talin-vinculin structural study. Reason: Talin is a core structural component of focal adhesions, linking integrins to actin; this is its principal location. Supporting Evidence: PMID:15070891 Talin interactions with vinculin are essential for focal adhesions. |
| GO:0005925 focal adhesion | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (ARBA, Ensembl, InterPro, SubCell) focal adhesion. Reason: Talin is a core structural component of focal adhesions, linking integrins to actin; this is its principal location. Supporting Evidence: PMID:11279249 Talin is a major link between integrin and the actin cytoskeleton and was shown to play an important role in focal adhesion assembly. |
| GO:0005925 focal adhesion | IMP PMID:26923917 Dual role of vinculin in barrier-disruptive and barrier-enha... | ACCEPT | Summary: IMP focal adhesion: talin-positive focal adhesions in endothelial cells. Reason: Talin is a core structural component of focal adhesions, linking integrins to actin; this is its principal location. Supporting Evidence: PMID:26923917 Thrombin treatment significantly increased the vinculin association with FA partner talin |
| GO:0005925 focal adhesion | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from chicken talin (P54939). Reason: Talin is a core structural component of focal adhesions, linking integrins to actin; this is its principal location. Supporting Evidence: PMID:11279249 Talin is a major link between integrin and the actin cytoskeleton and was shown to play an important role in focal adhesion assembly. |
| GO:0007043 cell-cell junction assembly | IEA GO_REF:0000117 | MODIFY | Summary: ARBA machine-learning annotation to cell-cell junction assembly. Reason: Talin assembles integrin-mediated junctions with the extracellular matrix, not cell-cell junctions; the cell-cell term is a misdirected generalization. Focal adhesion assembly captures the process talin actually performs. Proposed replacements: focal adhesion assembly Supporting Evidence: PMID:15494027 talin is essential for the assembly of such junctions PMID:15494027 The cytoskeletal proteins talin and vinculin form part of a macromolecular complex on the cytoplasmic face of integrin-mediated cellular junctions with the extracellular matrix. PMID:29880641 The AJ (containing cadherins and catenins) and FAs (comprising integrins, talin, and paxillin) differ in protein composition |
| GO:0007043 cell-cell junction assembly | TAS PMID:15494027 Cytoskeletal proteins talin and vinculin in integrin-mediate... | MODIFY | Summary: TAS from a review of talin and vinculin in integrin-mediated adhesion. Reason: The cited review states talin is essential for assembly of integrin-mediated junctions with the extracellular matrix, i.e. focal adhesions, not cell-cell junctions. Proposed replacements: focal adhesion assembly Supporting Evidence: PMID:15494027 talin is essential for the assembly of such junctions PMID:15494027 The cytoskeletal proteins talin and vinculin form part of a macromolecular complex on the cytoplasmic face of integrin-mediated cellular junctions with the extracellular matrix. |
| GO:0007155 cell adhesion | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro (IPR036723, vinculin/alpha-catenin-like bundle superfamily) to cell adhesion. Reason: Correct but general; talin is required for integrin-dependent cell adhesion. The specific process is cell-matrix adhesion. Supporting Evidence: PMID:35044719 Talinβ1 (TLN1) is a cytoplasmic adapter protein necessary for integrinβmediated cell adhesion |
| GO:0007229 integrin-mediated signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara transfer of integrin-mediated signaling pathway from mouse. Reason: Talin binding to integrin tails is the final step of inside-out integrin activation and also couples ligated integrins to the cytoskeleton; it participates in integrin signaling, but its core role is the adaptor and activator function. Supporting Evidence: PMID:16546176 Talin mediates integrin signaling by binding to integrin cytoplasmic tails through its FERM domain |
| GO:0009986 cell surface | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: UniProt SubCell mapping to cell surface. Reason: GO cell surface denotes the external part of the plasma membrane. Talin is a cytoplasmic protein on the inner face of the membrane, so plasma membrane and focal adhesion are the accurate locations. Supporting Evidence: PMID:15494027 The cytoskeletal proteins talin and vinculin form part of a macromolecular complex on the cytoplasmic face of integrin-mediated cellular junctions with the extracellular matrix. |
| GO:0009986 cell surface | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS from mouse talin-1 (P26039). Reason: GO cell surface denotes the external part of the plasma membrane. Talin is a cytoplasmic protein on the inner face of the membrane, so plasma membrane and focal adhesion are the accurate locations. Supporting Evidence: PMID:15494027 The cytoskeletal proteins talin and vinculin form part of a macromolecular complex on the cytoplasmic face of integrin-mediated cellular junctions with the extracellular matrix. |
| GO:0017166 vinculin binding | IPI PMID:15070891 Structural basis for amplifying vinculin activation by talin... | ACCEPT | Summary: IPI with vinculin (P18206): crystal structure of vinculin head bound to talin VBS1 and biochemical analysis of three VBSs. Reason: Talin vinculin-binding sites in the rod bind the vinculin head and activate vinculin. This is a core, conserved talin activity; a sponge talin VBS peptide likewise binds and activates sponge vinculin. Supporting Evidence: PMID:15070891 Talin interactions with vinculin are essential for focal adhesions. 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:0030036 actin cytoskeleton organization | IBA GO_REF:0000033 | ACCEPT | Summary: IBA actin cytoskeleton organization from PTN000463398. Reason: Talin links integrins to actin and, by activating vinculin, promotes reorganization of the actin cytoskeleton at 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:0030274 LIM domain binding | IPI PMID:10320340 Molecular interactions of N-RAP, a nebulin-related protein o... | KEEP AS NON CORE | Summary: IPI with N-RAP LIM domain (mouse Q80XB4) by solid-phase binding. Reason: A muscle-specific interaction at myotendon junctions and intercalated discs; real but peripheral to talin core function. Supporting Evidence: PMID:10320340 talin binds with high affinity to the LIM domain of N-RAP |
| GO:0032587 ruffle membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt SubCell mapping to ruffle membrane. Reason: Talin is found at membrane ruffles (colocalizing with LAYN) but its principal site is focal adhesions. |
| GO:0033622 integrin activation | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer of integrin activation from mouse talin-1. Reason: Talin head binding to the beta integrin tail is a final common step of inside-out integrin activation; in platelets loss of talin-1 abolishes alphaIIb beta3 activation. Supporting Evidence: PMID:23382103 lack of Talin-1 or Kindlin-3 in platelets has been shown to abrogate integrin Ξ± IIb Ξ² 3 activation with loss of platelet spreading and aggregation in vivo PMID:11279249 the interaction between integrin and talin was greatly enhanced by PI4,5P(2)-induced talin activation |
| GO:0034451 centriolar satellite | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: HPA immunofluorescence: centriolar satellite. Reason: Single high-throughput antibody localization; no functional link between talin and centriolar satellites is known. Retained as unconfirmed, non-core. |
| GO:0035091 phosphatidylinositol binding | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer of phosphatidylinositol binding from mouse. Reason: Talin binds PI(4,5)P2, which unmasks its integrin-binding site and targets it to the membrane; the term is general but correct. Supporting Evidence: PMID:11279249 the interaction between integrin and talin was greatly enhanced by PI4,5P(2)-induced talin activation |
| GO:0043622 cortical microtubule organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara transfer of cortical microtubule organization from mouse. Reason: Per UniProt (by similarity to mouse), talin with KANK1 organizes cortical microtubule stabilizing complexes at focal adhesion rims. Plausible, but a secondary role. |
| GO:0045296 cadherin binding | HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | MARK AS OVER ANNOTATED | Summary: HDA cadherin binding from an E-cadherin interactome proteomics study. Reason: Proximity/affinity proteomics captures many cytoskeletal neighbours of the cadherin complex. Talin does not have an established direct cadherin-binding activity and works at integrin-matrix adhesions. Supporting Evidence: PMID:29880641 The AJ (containing cadherins and catenins) and FAs (comprising integrins, talin, and paxillin) differ in protein composition |
| GO:0051015 actin filament binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro mapping to actin filament binding. Reason: Talin rod and I/LWEQ domain bind F-actin, forming the actin end of the integrin-actin linkage. Supporting Evidence: PMID:11279249 Talin is a major link between integrin and the actin cytoskeleton and was shown to play an important role in focal adhesion assembly. |
| GO:0051893 regulation of focal adhesion assembly | NAS PMID:15070891 Structural basis for amplifying vinculin activation by talin... | MODIFY | Summary: NAS regulation of focal adhesion assembly, from the talin-vinculin structural study. Reason: Talin is a structural component required for focal adhesion assembly rather than a regulator acting from outside; focal adhesion assembly is more accurate. Proposed replacements: focal adhesion assembly Supporting Evidence: PMID:15070891 Talin interactions with vinculin are essential for focal adhesions. PMID:15494027 talin is essential for the assembly of such junctions |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: HDA: talin-1 detected in exosome proteomes. Reason: Abundant cytoskeletal proteins are commonly detected in exosome preparations; this reflects cargo, not a talin function. |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: HDA: talin-1 detected in exosome proteomes. Reason: Abundant cytoskeletal proteins are commonly detected in exosome preparations; this reflects cargo, not a talin function. |
| GO:0070062 extracellular exosome | HDA PMID:21362503 Protein profile of exosomes from trabecular meshwork cells. | KEEP AS NON CORE | Summary: HDA: talin-1 detected in exosome proteomes. Reason: Abundant cytoskeletal proteins are commonly detected in exosome preparations; this reflects cargo, not a talin function. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: HDA: talin-1 detected in exosome proteomes. Reason: Abundant cytoskeletal proteins are commonly detected in exosome preparations; this reflects cargo, not a talin function. |
| GO:0070527 platelet aggregation | HMP PMID:23382103 Platelet proteome analysis reveals integrin-dependent aggreg... | KEEP AS NON CORE | Summary: HMP platelet aggregation: reduced talin-1 in MDS platelets associated with defective integrin-dependent aggregation. Reason: Talin-1 activates integrin alphaIIb beta3, which mediates platelet-platelet adhesion through fibrinogen; talin therefore participates in platelet aggregation, a tissue-specific application of its integrin-activation function. Supporting Evidence: PMID:23382103 lack of Talin-1 or Kindlin-3 in platelets has been shown to abrogate integrin Ξ± IIb Ξ² 3 activation with loss of platelet spreading and aggregation in vivo |
| GO:0098609 cell-cell adhesion | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA cell-cell adhesion from PTN000463398 (Drosophila rhea donor). Reason: Judged on human evidence: in humans talin works through integrins, which mostly attach cells to matrix but also mediate cell-cell adhesion (platelet aggregation via alphaIIb beta3, which GO places under cell-cell adhesion). The term is therefore defensible for human TLN1, unlike in a sponge where no such evidence exists, but cell-matrix adhesion is the core process. Supporting Evidence: PMID:23382103 lack of Talin-1 or Kindlin-3 in platelets has been shown to abrogate integrin Ξ± IIb Ξ² 3 activation with loss of platelet spreading and aggregation in vivo PMID:35044719 Talinβ1 (TLN1) is a cytoplasmic adapter protein necessary for integrinβmediated cell adhesion |
| GO:0007160 cell-matrix adhesion | TAS PMID:15494027 Cytoskeletal proteins talin and vinculin in integrin-mediate... | NEW | Summary: Proposed: talin participates in integrin-mediated adhesion of cells to the extracellular matrix. Reason: Talin does the work of cell-matrix adhesion: it binds integrin beta tails, activates integrins and physically links them to actin, and is essential for assembling junctions with the extracellular matrix. Comparator check: cytoplasmic integrin partners ITGB1BP1, LIMS1 and PPFIA2 carry this term in human GOA, so the term is used for intracellular participants. The existing annotations carry only cell adhesion and cell-cell adhesion. Supporting Evidence: PMID:15494027 The cytoskeletal proteins talin and vinculin form part of a macromolecular complex on the cytoplasmic face of integrin-mediated cellular junctions with the extracellular matrix. PMID:15494027 talin is essential for the assembly of such junctions PMID:35044719 Talinβ1 (TLN1) is a cytoplasmic adapter protein necessary for integrinβmediated cell adhesion |
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Download this section (compressed HTML)Q: Talin is common to amoebozoans and opisthokonts, where it predates integrins in some lineages. Does Capsaspora talin bind the NPxY motif of Capsaspora integrin beta2 and localize with integrin beta2 and vinculin in adhesive filopodia, i.e. was talin already an integrin adaptor before animals?
Q: Which talin activities are ancestral (actin binding, membrane/phosphoinositide binding, NPxY-tail binding) and which arose with the animal integrin adhesome (force-dependent cryptic vinculin-binding sites, KANK-mediated microtubule targeting)?
Q: Should the talin-family IBA for cell-cell adhesion (PTN000463398) be restricted to lineages with integrin-mediated cell-cell adhesion, given that talin core function is cell-matrix adhesion?
Experiment: Express the Capsaspora talin FERM head and test binding to Capsaspora integrin beta1-3 cytoplasmic tails (wild type and NPxY mutants) and to PI(4,5)P2 liposomes; test whether Capsaspora talin VBS peptides activate Capsaspora vinculin F-actin binding.
Type: Cross-species binding assay
Experiment: Rescue talin-1/talin-2 double-knockout mammalian cells with talins from sponge, Capsaspora and Dictyostelium and measure integrin activation, focal adhesion assembly and spreading on fibronectin.
Type: Genetic complementation
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